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2014 Volume 27 No.1
NEWSLETTER
ORGAN SPECIFIC AUTOIMMUNE DISEASES
Page
No.
4
5
Guest Editor
Dr. C. Balakrishnan
'When RBC Develop Cold Feet'
Cold Agglutinin Disease and the role of the
neglected parameter MCHC
Dr. Kunal Sehgal
Immune system protects us
from disease and infection.
When immune response is
11
Gut-specific Autoimmune Diseases
Dr. Philip Abraham
15
Primary Autoimmune Neurological Disorders
Dr. Roopkumar Gursahani
18
Auto Immune Diseases&Ocular Manifestations
Dr. Nisheeta Agarwala
22
Autoimmune Diseases of the Skin
Dr. Nina Madnani
25
27
31
generated against selfcomponents autoimmune
diseases
Autoimmune diseases
frequently pose a challenge in diagnosis and
treatment hence their knowledge is essential in
clinical practice. The Rheumatology team together
Adverse Effects of Immunosuppressive Therapy
Dr. Gurmeet Mangat
Laboratory Tests in Rheumatology
Dr. Rohini Samant
On the trail of diseases, years before
they strike - Auto antibodies
Dr. Vipla Puri
result.
with other specialists have contributed towards this
Newsletter issue on "Organ Specific Autoimmune
Diseases". We are privileged to have Dr. V. R. Joshi,
Emeritus Editor of Hinduja Newsletter to write the
preface for this issue.
Rheumatology Quiz
Dr. C. Balakrishnan
32
Our Team
33
P. D. Hinduja News
34
Welcome to P. D. Hinduja Hospital Pariwar
38
Editorial Board
Dr. Philip Abraham
Dr. Tester Ashavaid
Dr. C. Balakrishnan
Dr. Sudeep Shah
2
Editor
Dr. Reeta J. Dalal
Guest Editor
Dr. C. Balakrishnan
Editor Emeritus
Dr. V. R. Joshi
2014 Volume 27 No.1
Dr. Reeta J. Dalal
Consultant Physician
For Editorial Enquiries write to us at: [email protected]
Printed & Published at:
P D Hinduja National Hospital & Medical Research Centre
Veer Savarkar Marg, Mahim, Mumbai – 400016. (INDIA)
Tel.: +91-22-2445 1515/ 2444 2222/ 2444 9199 Fax: +91-22-24449151
Website: www.hindujahospital.com
PREFACE
The primary function of immune system is to protect
an individual from infection. It achieves this by
identifying the invading organism and destroying it
employing its (versatile) (awesome!) destructive
machinery. Immune system harbours the potential to
attack and destroy the host cells and tissues. This is
prevented by the induction of self-tolerance which is
achieved by eliminating cells with self reactive
potential. The elimination takes place during immune
cell maturation process in the thymus (T-cells) and bone-marrow (B-cells).
However, the elimination process is not perfect and a few weakly self reactive
cells escape the elimination process. These elements have the potential to
induce autoimmunity.
The development of autoimmunity however needs additional factors, namely
genetic susceptibility (to develop autoimmunity) and inciting environmental
agent(s) usually a microorganism. Once initiated the process becomes selfperpetuating, as the cellular destruction provides constant supply of antigens
against which autoimmunity has developed. Hence, autoimmune diseases
are persistent, incurable, associated with significant ill health and even early
death. Autoimmune process can be organ specific e.g. Hahimoto's thyroiditis
or diffuse and non organ specific e.g. systemic lupus erythematosus. Being
incurable, and with serious health issues, early diagnosis and initiation of
appropriate therapy (to control the disease) is of paramount importance.
Treatment involves corticosteroids (almost always in most situations) along
with chemotherapy with immunosuppressive drugs and recently with
biologics. Failure of treatment results in organ failure often necessitating
replacement therapy including organ transplantation.
This edition of the Newsletter provides information on organ specific
autoimmune disorders.
Dr. V. R. Joshi
M. D., Consultant Rheumatologist
and Director, Research, FICP (India)
2014 Volume 27 No.1
3
Guest Editor
Autoimmune diseases are a group of diseases where
the immune system turns on itself and causes
pathology to self- tissues.
Systemic auto-immune
diseases like Rheumatoid arthritis and Systemic Lupus
eythematosus are diseases that are being increasingly
recognized.
Autoimmune diseases limited to organs are also
common and increasingly seen and diagnosed. It is important to recognize
these diseases as their treatment includes the usage of steroids and other
immunosuppressive therapy.
This issue is dedicated to “Organ specific auto-immune diseases” afflicting
different organs systems. I hope it will enable the reader to familiarize himself
and approach these patients in a better way.
Dr. C. Balakrishnan
MD, Consultant Rheumatologist
4
2014 Volume 27 No.1
'When RBC Develop Cold Feet’
Cold Agglutinin Disease and the role of the neglected
parameter MCHC
Dr. Kunal Sehgal, Dr. Neha Lankhe
Hematology Department
Let us start by looking at Complete Blood Count (CBC)
results of cases 1 and 2 shown in Table 1. At the outset,
the striking thing is that there is a hemoglobin (Hb) and
hematocrit (HCT) mismatch. Normally HCT = 3 x Hb.
However, in the above scenario this relationship is not
maintained. This may rarely occur if sample is kept on
table for a long time and sample run on a machine
without mixing. However in current day automated
analysers with vacutainer collections, sample is
automatically mixed 8-10 times before aspiration as
was done in the two cases shown in Table 1.
reduced. In Iron Deficiency anemias it is on the lower
side of normal whereas in macrocytic anemias it is on
the higher side of normal. A MCHC reading of > 36 is
an uncommon finding and should alarm the CBC
operator.
The MCHC is known to >36 in hereditary spherocytosis
(HS). However all cases of HS may not have MCHC
>36 and typically MCHC because of spherocytosis will
not exceed 40. A high MCHC as shown in cases above
is typically seen when the red cells have agglutinated.
CBC Parameter
Case 1
Case 2
Reference range
RBC
0.84 X 1012
0.86 X 1012
4.5 - 6.5 X 1012 /L
Hb
7.3
7.9
13 - 18 g/dl
HCT
8.2
10.1
40 - 54
MCV
97.6
117.4
76 - 96 fl
MCH
86.9
91.9
27 - 32pg
MCHC
89
78.2
30 - 36 g/dl
RDW
20
28.2
11.5 - 14.5 %
TLC
8 X 10
PC
680 X 109
9
12.44 X 10
316 X 109
9
4 - 11 X 109 /L
150 - 400 X 109 /L
Table 1: CBC reports of cases 1 and 2 with Reference ranges
Having known that there is nothing wrong with the
machine the next striking result is the abnormally high
MCV and MCHC. The MCHC i.e. the Mean
Cell Hemoglobin Concentration is a derived parameter
in the automated analysers. It is derived from
the Hb and HCT according to the formula:
MCHC=(Hb/ HCT) x100.
Typically, MCHC remains in normal range in most
anemias as both Hb and HCT are proportionately
The agglutinated RBCs get counted together as one
large RBC, which explains the falsely low RBC count
and the high MCV, high MCH and the high MCHC. As
Hb is measured after lysing of RBCs, the Hb
measurement is correct but RBC count and HCT is
falsely low. MCHC falsely increases as numerator (Hb)
remains the same but denominator is markedly reduced
(HCT). Hence, if the MCHC is high (>36 g/dl),
peripheral smear of the sample must be examined for
2014 Volume 27 No.1
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'When RBC Develop Cold Feet’
Cold Agglutinin Disease and the role of the neglected parameter MCHC
presence of spherocytes or red cell agglutinates. If the
latter are found, the sample is kept in a water bath at
37ºC for an hour and re-analysed. Correction of RBC
count and indices and reduction or disappearance of
agglutinates on smear after warming of sample
suggests presence of cold agglutinins in the serum. As a
policy all samples in our laboratory with MCHC>36
CBC
Parameters
are re-run after one hour of warming at 37ºC in a water
bath.
Coming back to our index cases, the smears of both the
samples (cases 1 and 2) revealed red cell agglutinates
(Figure 1) and hence post-warming sample were
analysed which showed the following results:
Case 1
Pre-warming
12
Case 2
Post-warming
2.42 X 10
12
Pre-warming
0.86 X 10
12
Post-warming
RBC
0.84 X 10
1.53 X 10
Hb
7.3
8.3
7.9
8.0
HCT
8.2
22.6
10.1
17.8
MCV
97.6
93.5
117.4
116.3
MCH
86.9
34.2
91.9
52.3
MCHC
89
36.2
78.2
44.9
12
In case 1, all the RBC indices now show correction post
warming. In case 2, there is a partial correction only
and the smear showed RBC agglutinates even after post
warming, however the agglutination was much reduced
in severity. A work-up for cold agglutinin disease was
advised in both the cases.
Both case 1 and case 2 showed similar CBC findings
but had contrasting clinical profile as discussed below.
Case 1:
This was a 43 year old female who presented and fever
with chills since three weeks, cough with expectoration
and yellowish discoloration of urine. There was no
history of abdominal pain, clay colored stools,
dyspnea, oliguria or joint pain. She was diagnosed to
have malaria and treated for the same, however, fever
persisted. On examination, icterus was present, vitals
were stable and liver was soft, non-tender and mildly
enlarged. In addition to the CBC findings, discussed
earlier, other laboratory investigations revealed:
Reticulocyte count 10.8%
Total bilirubin 7.1 mg/dL (Direct: 4, Indirect: 3.1)
SGOT 101 IU (9-36) ; SGPT 39 IU (10-40)
ALP 303 IU (40-120) ; GGT 331 IU (0-60)
Red cell agglutinates seen on peripheral smear
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2014 Volume 27 No.1
CRP 192 mg/ dL
'When RBC Develop Cold Feet’
Cold Agglutinin Disease and the role of the neglected parameter MCHC
Chest X ray revealed fibrotic shadows in the right upper
zone, fibronodular shadows in the left upper zone with
left apical pleural thickening. In view of the presence of
cold agglutinins on peripheral smear, clinical history of
a febrile patient with suspected interstitial shadows on
chest X-rays, work up for mycoplasma pneumoniae was
advised. Anti M.Pneumoniae IgM was positive 16.77
NTU (>11 is positive). Bacterial cultures were negative.
Case 2
This was an 89 year old female, known case of
hypertension with ischemic heart disease and severe
osteoarthritis, who presented with a history of traumatic
fall with subsequent fracture of right femoral neck,
superior and inferior pubic rami. Laboratory
investigations revealed:
Total bilirubin 2.8 mg/dL (Direct: 2.5, Indirect: 0.3)
SGOT 15 IU (9-36) SGPT 11 IU (10-40)
ALP 54 (40-120) GGT 6 (0-60)
Total serum proteins 6.1g/dL (albumin 3,globulin 3.1)
Reticulocyte count 10.1%
Renal function tests normal
Coagulation profile normal
During Blood grouping and cross matching blood for
surgery, RBC antibody screening was positive, Direct
Coombs test was positive. In addition as discussed
earlier the CBC showed presence of RBC agglutinates
on the peripheral smear. Hence, the presence of a cold
antibody was confirmed and a search to rule out
malignancy and/ or infection was done.
Anti Mycoplasm Pneumoniae IgM was negative
(2.395 NTU)
Immunofixation electrophoresis revealed a
monoclonal gammopathy of IgM kappa type.
Serum kappa light chain: 1620 mg/dL (629-1350)
Serum lambda light chain: 562 mg/dL (313-723)
Thus, a diagnosis of CD5, CD10 negative B cell NHL
was offered. In view of the IgM kappa band on IFE, the
diagnosis was consistent with a lymphoplasmacytic
lymphoma.
Cold Agglutinin Disease
Introduction
Cold hemagglutination was first described by
Landsteiner in 1903. Cold agglutination disease (CAD)
is a type of autoimmune hemolytic anemia (AIHA) which
is characterized by an immune reaction against red
blood cell self-antigens. CAD has been classified into
primary (idiopathic) and secondary.
Etiology:
Primary Cold Agglutinin Disease is usually associated
with monoclonal cold-reacting autoantibodies, usually
chronic and occurs after the fifth decade of life.
Secondary Cold Agglutinin Disease is associated with
infectious or lymphoproliferative disorders.
Monoclonal secondary disease is usually chronic,
occurs in adults, while polyclonal is usually transient
and occurs in children and young adults.
Causes of the Secondary disease:
1. Neoplastic etiology
B-cell neoplasms - Waldenström
macroglobulinemia, Lymphoma, Chronic
Lymphoid Leukemia, Myeloma
Nonhematologic neoplasms
2. Infectious etiology
Mycoplasma infections -M. pneumoniae
Viral infections - Infectious mononucleosis due to
Epstein-Barr virus (EBV) or CMV, Mumps,
Varicella, Rubella, Adenovirus, HIV, Influenza,
Hepatitis C
Bacterial infections - Legionnaire disease,
Syphilis, Listeriosis, Escherichia coli
Parasitic infections - Malaria, Trypanosomiasis
Kappa: lambda ratio was 2.88 (1.47-2.95).
Bence Jones proteins were absent in urine.
Pathogenesis:
Bone marrow examination revealed a hypercellular marrow with 18% lymphocytes which on
flow cytometric immunophenotyping comprised of
kappa restricted B cells expressing CD 19, CD 20,
CD 22 and heterogenous FMC7 while they were
negative for CD5, CD10, CD23, CD11c, CD103,
Cd25, CD123, CD2, CD3, CD4, CD7 and CD8.
Cold agglutinins may be found in the sera of healthy
subjects as well as in patients with cold AIHA. Cold
agglutinins bind to erythrocyte surface antigens at a
temperature optimum of 0 to 4ºC. In contrast to
polyclonal agglutinins in healthy individuals,
monoclonal agglutinins often have high thermal
amplitude, which contributes to their pathogenicity at
temperatures approaching 37ºC. Benign cold
2014 Volume 27 No.1
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'When RBC Develop Cold Feet’
Cold Agglutinin Disease and the role of the neglected parameter MCHC
agglutinins occur in titers which are less than 1:64 at
4ºC and they have no activity at higher temperatures,
while pathologic cold agglutinins typically have titers
well over 1:1000 and they may react at 28 to 31ºC or
even up to 37ºC.
In the great majority of CAD patients, the cold
agglutinins are of the IgM kappa type and are specific
for the I antigen, an erythrocyte surface carbohydrate
macromolecule.
During passage through acral blood vessels, cooling
allows IgM cold agglutinin to bind to erythrocytes,
causing agglutination and binding of complement C1
complex. C1 esterase activates C4 and C2, generating
C3 convertase which binds and splits C3, leading to
deposition of C3b on the erythrocyte surface. Upon
subsequent warming, IgM dissociates from the cell
surface and the agglutinated cells are detached from
each other, while C3b remains bound. C3b may in turn
activate C5, leading to the formation of the membrane
attack complex and intravascular cell lysis. Most
destruction of C3b-coated erythrocytes is mediated by
reticulo-endothelial cells in the liver. Intrahepatic
conversion of C3b is responsible for the deposition of
C3d on the surviving erythrocytes which are released
into the systemic circulation.
Clinical presentation and diagnosis:
Mild chronic hemolytic anemia exacerbates in the
winter. Acrocyanosis and Raynauds phenomenon occur
due to the agglutination of cells in the cooler vessels of
the hands and feet. In few cases, a palpable spleen
suggests a lymphoma or infectious mononucleosis. The
paradox in CAD is the exacerbations that occur during
febrile illnesses. This is because majority of the CAD
patients have low levels of C3 and C4 during their
steady states, due to continuous complement
consumption. During acute phase reactions, the C3
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2014 Volume 27 No.1
and C4 levels increase due to their enhanced
production, resulting in the exacerbation of hemolysis.
Diagnostic workup:
The first suspicion of CAD comes from the hematology
laboratory's failed attempts to obtain a meaningful RBC
count and indices. The RBC counts are decreased and
MCV is falsely elevated, producing an unbelievably
high MCHC, which can be rectified by prewarming the
samples to 37ºC before feeding them into the analyzer.
Patients may present with leucopenia and
thrombocytopenia (due to presence of the I antigen on
these cells).
Whenever cold agglutinins are picked up on peripheral
smear, a cold agglutinin disease workup is advised
which should include a reticulocyte count, bilirubin
levels (which may be mildly elevated) and direct
antiglobulin test which is generally positive with
polyspecific and anti- compliment antisera
(C3d alone > C3d+IgG > IgG alone). A titre for the
cold agglutinin antibodies may also be determined. In
addition a serum protein electrophoresis with
immunofixation electrophoresis is advised to rule out
presence of paraproteins. If the patient is febrile and
suspected to have interstitial pneumonia, a work up for
Mycoplasma Pneumoniae and/or other viral markers
may be required.
Take home message:
In all CBC samples with MCHC >36, blood smear
should be examined to rule out red cell agglutination,
and ideally the sample rerun after warming at 37°C
for one hour
CAD work up should include Reticulocyte count,
Direct Coomb's test, serum protein electrophoresis
with IFE along with work up for other etiological
factors based on clinical history and findings.
2014 Volume 27 No.1
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2014 Volume 27 No.1
Gut-specific Autoimmune
Diseases
Dr. Philip Abraham, Dr. Abhijit Deshmukh & Dr. Meghraj Ingle
Gastroenterology Department
Case History
A 27-year-old man with 3-month history of diarrhea
with intermittent rectal bleeding was referred for
evaluation. On examination, he had diffuse abdominal
tenderness and no organomegaly. Laboratory
investigations: hemoglobin 10.5 g/dL, ESR 45 mm in
1st hour, stools showed 20-25 WBC and 10-15
RBC/hpf, stool culture was negative.
Colonoscopy was done in view of the long history. It
showed continuous inflammation and ulceration and
friability from the anal verge up to 35 cm with a sharp
cut-off, the mucosa above appeared normal, as did the
terminal ileum. Histology of the biopsy specimen
showed changes of chronic colitis with activity. TB
culture was negative.
Discussion
Ulcerative colitis
Ulcerative colitis is an inflammatory bowel disease (IBD)
characterized by abdominal pain and diarrhea with
episodes of blood with the stools. Although it can start
at any age, it usually affects people in the 20s and 30s.
The disease affects only the mucosa of the large
intestine, starting at the rectum and extending
proximally for variable extents. Symptoms vary
depending on the severity and extent of inflammation.
Rectal disease usually presents with bleeding in stools
and tenesmus. When the colon is involved, it presents
with abdominal cramping and pain, and sometimes
weight loss. The diagnosis is made on colonoscopy and
histology.
The course of ulcerative colitis varies, with periods of
acute illness usually alternating with remission.
Fulminant colitis is a rare life-threatening form affecting
the entire colon and causing severe pain, profuse
bloody diarrhea and, sometimes, dehydration and
shock; these patients are at risk of serious
complications, including toxic megacolon and colon
perforation. Other possible complications of ulcerative
colitis include severe bleeding, anemia, extraintestinal
manifestations (jaundice, arthritis, osteoporosis,
episcleritis) and increased risk of colon cancer.
The goal of medical treatment is to control the
inflammation and so prevent complications.
Formulations of 5-aminosalicylic acid (5-ASA) like
sulfasalazine, mesalamine, balsalazide and olsalazine
are used as first-line therapy. These drugs can relieve
symptoms in more than 90 percent of patients; those
with only proctitis may be controlled with 5-ASA
suppositories alone. Left-sided colitis may respond to
mesalamine enemas, alone or in combination with the
oral drug. Corticosteroids are used when this treatment
fails. Immune-suppressor drugs like azathioprine are
used as steroid-sparing agents, when the requirement
for the latter exceeds safe limits. Cyclosporine is a
potent drug that is reserved for those who have not
responded to the other medications or may otherwise
need surgery. Biologic agents such as infliximab are
reserved for resistant cases. Surgery is curative for the
colonic disease but carries its own morbidity.
Crohn's disease
Like ulcerative colitis, Crohn's disease is also an IBD, but
marked by inflammation of all layers of the intestine.
Depending on the region of involvement (in India,
usually the ileo-cecal region or the large or small
intestine, with normal mucosa alternating with affected
segments), it presents with abdominal pain, diarrhea,
fever and at times malnutrition and delayed growth or
sexual development in children. Complications of this
ulcerating disease include bowel obstruction, internal
fistulae, rarely bleeding and anal fissures.
Extraintestinal features include fatigue, arthritis, eye
inflammation, skin disorders and hepatitis or
cholangitis.
Blood tests usually show anemia and elevated Creactive protein level. Colonoscopy might show
ulcerated segments with skip areas in between.
Histology often shows only non-specific changes of
chronic inflammation but may show granulomas. The
imaging and histology findings are almost identical to
those of tuberculosis, to the extent that only culture for
mycobacteria and / or a trial of anti-TB treatment may
help to differentiate the two conditions. Other tests like
barium studies, CT or MR enteroclysis, capsule
enteroscopy or balloon enteroscopy are done to locate
the disease and areas of stricture in the small bowel
2014 Volume 27 No.1
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Gut-specific Autoimmune Diseases
(capsule enteroscopy should be avoided when
narrowing is suspected) and also to check for
complications such as fistulae or abscesses.
Medical treatment begins with the use of mesalamine
formulations. Corticosteroids are used in case of
moderate to severe inflammation that does not respond
to mesalamine. The corticosteroid budesonide has
fewer side-effects and may be preferred in those with
isolated ileo-cecal disease. Azathioprine is the most
widely used immunosuppressant and may even be
considered as first-line therapy, although the onset of
action is slow and the drug is a weak suppressant.
Infliximab and newer biologic agents (adalimumab,
certolizumab) are indicated in adults and children with
moderate to severe disease who do not respond to or
cannot tolerate other treatments. Methotrexate and
cyclosporine have been tried in patients not responding
to the routine immunosuppresants and in whom the
biologic agents cannot be used. It must be remembered
that potent drugs (immune suppressants, biologics)
carry risks of severe infections and malignancies on
long-term use. Antibiotics like metronidazole and
ciprofloxacin may help heal fistulae and abscesses.
Surgery is generally kept as a last resort in patients with
intractable disease with fistulae, abscesses and
strictures not responding to optimal medical therapy.
One principle of surgery is to be as conservative as
possible; the chance of disease recurrence after surgery
is quite high.
Celiac disease
Celiac disease is characterized by chronic inflammation
of the small intestinal mucosa. There is a strong genetic
predisposition, with major risk attributed to HLA-DQ2
and HLA-DQ8. Dietary proteins present in wheat,
barley and rye, commonly known as glutens, interact
with these HLA molecules to activate an abnormal
mucosal immune response and induce tissue damage.
Clinical manifestations are highly variable, may present
at any age, and involve multiple organ systems;
prolonged delays in diagnosis are therefore common.
Gastrointestinal manifestations may include diarrhea,
vomiting, abdominal pain, bloating and distention,
anorexia and constipation; weight loss or failure to
grow are prominent features. It is common for Celiac
disease to present with extraintestinal manifestations,
sometimes with little or no gastrointestinal symptoms;
examples include dermatitis herpetiformis, irondeficiency anemia, unexplained short stature, delayed
puberty, infertility, recurrent fetal loss, osteoporosis,
vitamin deficiencies, fatigue, protein-calorie
malnutrition, and elevated transaminases.
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2014 Volume 27 No.1
There is no one test that can definitively diagnose or
exclude celiac disease in every individual.
Characteristic lesions on small-intestinal biopsy include
atrophy of villi, crypt hyperplasia, and increased
intraepithelial lymphocytes. Serological tests like IgA
antihuman tissue transglutaminase (tTG) and IgA
endomysial antibody immunofluorescence (EMA) have
high sensitivity and specificity. Two major endoscopic
features are the disappearance or reduction of
Kerckring folds and the scalloped configuration of
reduced folds. These findings are however not specific.
Complications typically develop after many years of
disease. These include refractory Celiac disease,
ulcerative jejunoileitis, non-Hodgkin lymphoma, and
enteropathy-associated T-cell lymphoma.
The only proven treatment is strict and life-long
adherence to a gluten-free diet. All foods and drugs that
contain gluten from wheat, rye, barley and their
derivatives must be eliminated. Treatment of vitamin
and mineral deficiencies including iron, calcium,
phosphorus, folate, B12, and fat-soluble vitamins
should also be taken care of. Steroids and other
immunosuppressive agents can be tried in refractory
Celiac disease, i.e., those who do not respond to
complete exclusion of gluten in the diet.
Autoimmune Pancreatitis (AIP)
Autoimmune pancreatitis (AIP) is a rare malepredominant disease occurring at median age of over
45 years. A common clinical presentation is recurrent
acute pancreatitis or chronic pancreatitis, and rarely as
a pancreatic mass. The disease may be accompanied
by inflammation of the bile duct as well. AIP is known to
be associated with inflammation of the salivary glands,
retroperitoneal fibrosis, and tubulointerstitial nephritis.
AIP is now thought to be the pancreatic manifestation of
a systemic disease called IgG4-associated systemic
disease, which presents with unexplained fever, raised
inflammatory markers, and fibrosis in and around
organs. Pancreatic biopsy shows abundant lymphocytic
and plasma cell infiltration, marked swirling (storiform)
fibrosis, and obliterative phlebitis around the
pancreatic duct. Immunohistochemical determination
of IgG4-positive plasma cells is a useful adjunct to the
serological (elevated IgG4 level) and histological
diagnosis of AIP.
Although AIP is uniquely steroid-responsive, knowledge
of the natural history and treatment of refractory disease
is limited. Immune modulators like azathioprine and
mycophenolate mofetil are used to reduce the steroid
dose and side-effects.
Gut-specific Autoimmune Diseases
Autoimmune Hepatitis (AIH)
Patients with autoimmune hepatitis (AIH), usually
middle-aged women, may present with non-specific
symptoms such as lethargy, low fever, anorexia and
nausea with accompanying jaundice, anemia and joint
aches. Some may present like an acute hepatitis, and
previous such episodes in history should raise the
suspicion of AIH. The presence of associated
autoimmune disorders including hemolytic anemia,
thyroiditis, arthritis, ulcerative colitis, and the sicca
syndrome adds to the possibility. Some patients may
present in the late stage as cirrhosis with its
complications.
Three main types have been identified. Type 1 is
common in women between the ages of 15 and 40
while type 2 primarily affects young girls; type 3 affects
children. The diagnosis is based on the presence of
autoantibodies in the blood, like antinuclear antibodies
(ANA), anti-smooth muscle antibody (ASMA) and antiLKM1 antibody and by ruling out other common causes
of chronic hepatitis. Liver biopsy not only confirms the
diagnosis but also helps in determining the stage of the
disease.
The mainstay of treatment is steroid, with most people
needing to continue the drug for years and sometimes
for life. Azathioprine is added to reduce the steroid
dose. Management of late-stage disease is similar to
that of cirrhosis of any etiology.
Primary Sclerosing Cholangitis (PSC)
Primary Sclerosing Cholangitis (PSC) is a chronic liver
disease characterized by cholestasis, with inflammation
and fibrosis of the intra- and extra-hepatic bile ducts. A
large majority (75%-90%) of patients also have IBD;
however, only approximately 4% of patients with IBD
have or develop PSC. Two-thirds of patients are men,
with mean age at diagnosis around 40 years. About a
third of patients are asymptomatic and detected during
screening of patients with ulcerative colitis who have
elevated alkaline phosphatase levels.
Symptoms upon initial presentation include fatigue,
jaundice, pruritus and right upper quadrant pain.
Recurrent febrile episodes of bacterial cholangitis occur
in 10%-15% of patients during the course of PSC.
Cirrhosis, portal hypertension and liver failure are endresults of a progressive disease.
Liver function tests reveal raised alkaline phosphatase
levels that are 3-5 times the reference range value.
Serum aminotransferase levels are increased but not
markedly so. Serum bilirubin level, predominantly the
conjugated component, is usually increased.
Hypergammaglobulinemia is present in 30% of
patients. Serum autoantibodies are detected in a
majority of patients: antineutrophil cytoplasmic
antibodies (ANCA) in 87%, anticardiolipin antibodies
in 66%, ANA in 53%. These patients have an increased
prevalence of HLA-B8, HLA-DR3, and HLA-Drw52a.
ERCP was considered the gold standard for diagnosis;
features include multiple strictures and dilatations of the
intra- and extrahepatic biliary ducts. MRCP is now the
preferred alternative. Liver biopsy is rarely required and
shows concentric fibrosis with obliteration of the small
ducts (obliterative fibrous cholangitis); this finding is
virtually diagnostic but is found in fewer than 10% of
biopsy specimens.
There is no curative medical therapy; the goals of
medical management are to treat the symptoms and to
prevent or treat the known complications. Therapies
that have been tried include ursodeoxycholic acid
(UDCA), which suppresses hepatic synthesis and
secretion of cholesterol and inhibits intestinal
absorption of cholesterol but also has a cytoprotective
effect; this may lead to decreased cholestasis and
improved liver functions. However, results are not
satisfactory. Cholestyramine forms a nonabsorbable
complex with bile acids in the intestine, which in turn
inhibits enterohepatic reuptake of intestinal bile salts,
reduces excess bile acids deposited in dermal tissue,
and decreases pruritus. Antihistamines can also be
used for pruritus. Immunosuppressive therapy has been
tried with disappointing results. Balloon dilatation and
stent placement can be done for blockages in the larger
bile ducts. Liver transplantation is the only effective
therapy and is indicated in end-stage liver disease.
Cholangiocarcinoma occurs in association with PSC in
6%-30% of patients. PSC is also a risk factor for colon
cancer in patients with ulcerative colitis. The median
length of survival from diagnosis to death or liver
transplantation is 10-15 years.
Primary Biliary Cirrhosis (PBC)
Primary Biliary Cirrhosis (PBC) is a chronic and
progressive cholestatic disease of the liver. The major
pathology is destruction of the small and medium sized
bile ducts, which leads to progressive cholestasis and
often end-stage liver disease. Duct destruction is
progressive, and is mediated by activated CD4 and
CD8 lymphocytes. Subsequent to the loss of the
intrahepatic bile ducts, a disruption of the normal bile
flow occurs with retention and deposition of toxic
substances that are normally excreted into bile.
2014 Volume 27 No.1
13
Gut-specific Autoimmune Diseases
Frequently a disease of women, it occurs between the
fourth and sixth decades of life; 25% are incidentally
diagnosed during a routine blood evaluation. Fatigue is
the first reported symptom. No correlation exists
between this symptom and the stage of the liver disease.
Pruritus is present in more than 50% of the patients, and
10% experience severe pruritus. Right upper quadrant
discomfort occurs in 20% of patients. Physical
examination may reveal jaundice, hyperpigmentation,
xanthelasmata, xerophthalmia, xerostomia, features of
the sicca syndrome, hepatomegaly and splenomegaly.
The hallmark of this disease is the presence of
antimitochondrial antibodies (AMA), found in 90%95% of patients, and they have a specificity of 98%.
Significant elevations of serum alkaline phosphatase
(ALP), Gamma-glutamyl transpeptidase (GGTP), and
immunoglobulin levels (mainly immunoglobulin M)
are the prominent lab abnormalities. Alanine
a m i n o t r a n s f e r a s e ( A LT ) a n d a s p a r t a t e
aminotransferase (AST) levels may be elevated.
Hypercholesterolemia with high HDL levels are also
found. The diagnosis is established or confirmed by
liver biopsy, which reveals chronic, non-suppurative,
destructive cholangitis of the small interlobular bile
ducts, lymphocytic and plasma cell infiltration, with
eosinophilic condensation in the portal tracts.
The goals of treatment are to slow the progression of the
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2014 Volume 27 No.1
disease and alleviate symptoms. UDCA is the major
medication used to slow the progression especially
early in the course of the disease. Immunosuppressants
have been tried but with varying results. The agents
used to treat pruritus are antihistamines,
cholestyramine and colestipol, rifampin, and opioid
agonists; pruritus is often refractory to medical therapy
and significantly impacts quality of life. Plasmapheresis
has also been tried for patients with severe pruritus
intractable to medical treatment.
Complications like hypercholesterolemia,
osteoporosis, renal tubular acidosis, and
hepatocellular carcinoma can occur. Liver
transplantation is the only life-saving procedure.
Gut-specific autoimmune diseases
Ulcerative colitis
Crohn's disease
Celiac disease
Autoimmune Pancreatitis (AIP)
Autoimmune Hepatitis (AIH)
Primary Sclerosing Cholangitis (PSC)
Primary Biliary Cirrhosis (PBC)
Primary Autoimmune Neurological
Disorders
Dr. Roopkumar Gursahani
Neurology Department
Case History:
A 35 year old lady saw us for stumbling gait and a
tendency to fall of 10 years duration. There was
episodic fluctuation of her vision. Three months prior to
the consult she developed upper respiratory infection
and felt that her neurological disability worsened after
that. She could not hold objects in her hands and
complained of tremors and severe exhaustion. Since
that time she had noticed pains on left and then right
side of the body. Then, the patient abruptly developed a
right hemisensory deficit after several days of work. The
MRI scan was performed at that time and revealed a
multifocal white matter disease - areas of increased T2
signal in both cerebral hemispheres. Spinal tap was
also done which revealed the presence of oligoclonal
bands in CSF. Visual evoked response testing was
abnormal with slowed conduction in optic nerves.
Gradually she developed weakness and numbness on
the right side, impaired urinary bladder function and
incontinence.
On examination: There was decreased hearing on the
left, and numbness in the right face, which extended
down into the entire right side. The Weber test revealed
greater conductance to the right. Rinne's test revealed
air greater than bone bilaterally. Tongue movements
were slowed, but tongue power appeared to be intact.
All the other cranial nerves were normal.
There was normal strength in the upper extremities
throughout. However, rapid alternating movements
were decreased in both upper extremities and the
patient had dysdiadochokinesia in the left hand. Mild
paraparesis was noted in both legs without severe
spasticity. Deep tendon reflexes were +2 and
symmetrical in the arms, +3 at the ankles and at the
knees. Bilateral extensor toe sign were present. Sensory
exam revealed paresthesia on the right to touch and
decreased pin sensation on the right diffusely. The
patient had mild vibratory sense loss in the distal lower
extremities. Romberg's was negative. Tandem gait was
mildly unstable.
Discussion
The above history is typical for a neurological condition
called multiple sclerosis. It belongs to a group of
diseases which primarily affect the nervous system and
have auto-immunity as its basis.
Multiple sclerosis (MS): It is a disabling neurological
disease affecting the young and is regarded as an
organ- specific inflammatory disease resulting from an
aberrant immune attack on myelin or myelin-producing
oligodendrocytes present in the central nervous system.
Acute onset of focal neurological deficit may herald the
onset of MS. Pathological hallmark of MS is the cerebral
or spinal plaque, which consists of a discrete region of
demyelination with relative preservation of axons.
However, spectroscopic and pathological studies
suggest some axonal loss may be an integral part of
disease process. Histological examination of active
plagues reveals perivascular infiltration of
predominantly T lymphocytes and macrophages and
occasionally plasma cells. Cranio-spinal MRI with
contrast detects old and new plaques. CSF may be
inflammatory in the acute stage. The back bone of
t r e a t m e n t s t i l l r e m a i n s s t e r o i d s . Va r i o u s
immunomodulatory agents including interferons,
glatiramer acetate, alemtuzumab, mitoxantrone are
often added to the regimen in case the disease is
recalcitrant.
Other common/important autoimmune neurological
diseases are:
Myasthenia Gravis: It is a disease of neuromuscular
junction characterised by fatigable weakness of
voluntary muscles. It is due to antibodies against
postsynaptic muscle membrane. World wide
prevalence is about 1/25000 population. It can occur
throughout the life with, bimodal peak of incidence in
younger women (second and third decade) and older
men (in fifth and sixth decade). Common symptoms
include easy fatigability, diplopia, dysphagia, dysarthria
and dyspnea which are particularly worse after exercise
and in the later part of the day, while the patient feels
better after rest. Patients may present in acute
myasthenic crisis with acute respiratory failure and may
need ventilator support. Diagnostic tests done include
neurophysicological tests like repetitive nerve
stimulation, single fibre EMG (SFEMG) and blood tests
2014 Volume 27 No.1
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Primary Autoimmune Neurological disorders
like anti-acetylcholine receptor antibodies.
Pyridostigmine, steroids, plasma exchange and
immunoglobulins constitute various treatment options.
In young patients, associated thymoma should be ruled
out by doing a CT scan of the thorax.
Lamber Eaton Myasthenic Syndrome: This
immunological disorder of nervous system is clinically
similar to myasthenia gravis but antibodies are directed
against presynaptic nerve terminal. The antibodies are
directed against P/Q type voltage gated calcium
channel present in nerve terminal. Diagnostic methods
include the same battery of tests as mentioned in
myasthenia gravis. This peculiar disorder often is
associated with some malignancies, especially small
cell lung cancer. Hence apart from confirming the
diagnosis based on characteristic EMG/NCV pattern,
effort must be made to rule out an underlying
malignancy. Treatment include 3, 4 diaminophyridine
with or without pyridostigmine along with the treatment
of malignancy if detected. Plasma exchange and
intravenous immunoglobulins are indicated in patients
presenting in crisis.
Neuromyelitis optica (NMO): This peculiar
neurological disorder is characterized by long segment
cord demyelination with or without optic neuritis and
demyelination in the brain. The definite prevalence is
not known, but probably NMO is more common in
eastern countries including India compared to the west.
Presentation may be acute or subacute. The MRI
changes are characteristic and detection of serum
aquaporin 4 antibodies in the serum contributes to the
confirmation of diagnosis. This antibody is IgG
antibody binding to complement leading to conclusion
that this is humoral disease in contrast to cellular
immune mechanism proposed for multiple sclerosis.
Treatment options include various types of
immnunomodulations like intravenous steroid pulse,
immunoglobulins and plasma exchange. Rituximab
has been tried for prevention of relapse in anecdotal
case reports.
Acute disseminated encephalomyelitis (ADEM):
This is a monophasic demylinating illness characterised
by multifocal CNS demyelination with encephalopathy
as a prominent feature. Disease may start as a post
infectious (most commonly measles) or post
vaccination process. CSF is inflammatory with
lymphocytic pleocytosis. Treatment options are usual
immunomodulatory therapies.
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2014 Volume 27 No.1
Acute and Chronic Inflammatory demyelinating
Polyneuropathies: Acute and chronic inflammatory
demyelinating polyneuropthies (AIDP & CIDP) are
autoimmune neurological disorders that cause
progressiveness motor sensory weakness and a loss of
sensation in the legs and arms. The pathogenesis is
uncertain but molecular mimicry has been suggested.
These disorders are diagnosed with electrophysiology
studies showing slow nerve conduction velocities,
variable velocities among nerves and prolonged
latencies of F-waves. Treatment modalities in AIDP
include intravenous immunoglobulins and plasma
exchange. Patients with respiratory insufficiency may
need ventilatory support. Treatment for CIDP consists
of conticosteroids such as prednisolone and nonsteroidal immunosuppressants such as cyclosporine A
and methotrexate. When immunosuppressive
treatments are inadequate, patients are treated with
intravenous immunoglobulins and plasmapheresis.
Issacs syndrome: This disease in characterized by
twitching, spasms and rippling of the muscles
(myokymia) as a result of hyper excitablility of motor
nerve fibers. Advanced cases manifest with generalized
stiffness and weakness. Most cases are idiopathic, but
a paraneoplastic variety is described where antibodies
are found against voltage gated potassium channel.
Few cases have been reported in association with
polyneuropathy and thymoma.
Phenytoin and
carbamazepine abolish continous muscle fiber activity.
Paraneoplastic variety responds to plasma exchange
which, can be tried in resistant idiopathic varieties as
well.
Stiff person syndrome: This condition is
characterized by persistent and intense spasms
particularly in proximal lower limbs and lumbar paraspinal muscles. Muscles of respiration and swallowing
may be involved in advanced cases. About two third
cases are associated with circulating autoantibodies to
enzyme glutamic acid decarboxylase, an enzyme
involved in synthesis of GABA. This condition is
associated with other autoimmune disorders like
pernicious anemia, thyroiditis and vitiligo. Diazepam is
particularly useful in relieving the spasms while
immunomodulation is useful for preventing
recurrences.
Primary Autoimmune Neurological disorders
Autoimmune Neurological Diseases




Myasthenia Gravis
 Acute and Chronic Inflammatory demyelinating
Lamber Eaton Myasthenic Syndrome
Polyneuropathies
Neuromyelitis optica (NMO)
 Issacs syndrome
Acute disseminated encephalomyelitis (ADEM)  Stiff person syndrome
2014 Volume 27 No.1
17
Auto Immune Diseases &
Ocular Manifestations
Dr. Nisheeta Agarwala, Dr. Prajakta Salunkhe
Ophtalmology Department
Autoimmune diseases are of two types:
1. Autoimmune diseases limited to eye.
2. Autoimmune diseases with systemic
involvement.
needed. Dapsone or a combination of steroid and
cyclophosphamide are the first line of treatment. The
treatment is continued till there is disease remission and
then the drugs are gradually reduced and stopped.
It is not uncommon for an ophthalmologist to see a
patient complaining of recurrent either painless or
painful blurring of vision, redness or dryness of eyes.
These symptoms can be manifestations of underlying
autoimmune disease. Many a times these ocular
symptoms can be associated with joint pains, dryness of
mouth, skin lesions and sometimes these ocular
symptoms are the only presenting symptoms. Such
cases must be referred to clinicians for a systemic work
up.
Mooren's Ulcer
Recurrent ocular episodes, if left untreated can lead to
visual disturbances or permanent ocular damage.
These cases must be treated with a combined
approach, of an ophthalmologist and a physician
trained in immunology.
Ocular Pemphigoid
The patients usually present with redness, discomfort,
grittiness and dryness in the eyes. The condition persists
for many years with periods of spontaneous remission
and flare-ups. Over a period of time there is scarring of
the cornea with reduction of vision. There can be
involvement of the mouth and skin as well.
This is a rapidly progressive, extremely painful,
ulcerative keratits which affects the peripheral cornea
and spreads circumferentially and then centrally. It is
not associated scleritis and there is no associated
diagnosable systemic disorder detected. The cause is
not known but this is an autoimmune disease directed
against specific target molecule in the corneal stroma ,
probably triggered in genetically susceptible
individuals. Clincially, there is peripheral ulceration
involving superficial 1/3rd of cornea, progressive
stromal thinning, vascularization of the stromal bed and
scarring. Initially topical steroids, cyclopegics and
prophylactic antibiotic are tried. If these fail, systemic
immunosuppressive therapy is used. If all else fails
surgical therapy like superficial lamellar keratectomy or
penetrating keratoplasty is contemplatedespecially if
there is perforation.
Management includes local steroid drops to reduce
inflammation and preservative free lubricants to keep
the eyes moist. Systemic immunosuppresants may be
Mooren's Ulcer
Peripheral Ulcerative Keratitis
Ocular Pemphigoid
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2014 Volume 27 No.1
This is characterized by severe, persistent peripheral
corneal infiltration, ulceration or thinning unexplained
by co-existent ocular disease. There is an underlying
autoimmune disease due to which there is immune
Auto Immune Diseases & Ocular Manifestations
cellular infiltration of scleral and episcleral tissues. This
can be infectious or associated with systemic
autoimmune disorders, including rheumatoid arthritis,
systemic lupus erythematosus, relapsing polychondritis,
spondyloarthropathies, Wegener granulomatosis,
polyarteritis nodosa and giant cell arteritis. It can be
classified into anterior and posterior scleritis. Anterial
scleritis - can be diffuse, nodular, necrotizing with
inflammation and necrotizing without inflammation
(scleromalacia perforans).
Peripheral Ulcerative Keratitis
complex deposition in peripheral cornea. The auto
antibodies may target sites in the corneal epithelium.
Associated systemic diseases include rheumatoid
arthritis, Wegener's granulomatosis, relapsing
polychondritis and systemic lupus erythematosis.
Treatment includes high dose systemic steroids and
immunosuppresants. Keratoplasty is done either as an
emergency in the event of a corneal perforation or
electively to restore vision.
Posterior scleritis is characterized by flattening of the
posterior aspect of the globe, thickening of the posterior
coats of the eye and retro bulbar edema.
Infectious scleritis requires appropriate treatment
depending on the organism. Non infectious scleritis
requires non-steroidal anti-inflammatory drugs
(NSAIDs), corticosteroids, or immunomodulatory
drugs. Rarely scleral grafts are required.
Episcleritis
Patient presents with acute onset redness and mild pain
in one or both eyes, typically in young adults. History
recurrent episodes is common. On examination there
Scleritis
Uveitis
Episcleritis
is no discharge only sectoral redness of one or both
eyes is seen with engorgement of episcleral vessels.
These vessels are large and more radial in directions
beneath the conjunctiva. If mild, episcleritis is treated
with artificial tears qid. Moderate to severe episcleritis
is treated with mild topical steroids.
Scleritis
This is a chronic, painful and potentially blinding
inflammatory disease characterized by edema and
Uveitis (inflammation of the uveal tract) is an eye
condition that can occur as an autoimmune disorder or
as a result of injury, infection or exposure to toxins. It is
classified into three groups:
(1) Anterior if it affects the anterior part of the uvea
-the iris (Iridocyclitis)
(2) Intermediate if it affects the middle or vitreous get
portion of the eye
(3) Posterior if it affects the retina and/or the choroids.
The term "pan-uveitis" is used if all three
compartments of the eye are affected.
The condition can be asymptomatic or present with
modestly diminished vision that is slowly progressive,
accompained with floaters. Vitritis is characterized by
2014 Volume 27 No.1
19
Auto Immune Diseases & Ocular Manifestations
Uveitis
Birdshot Retino Choroidopathy
accumulation of inflammatory exudates in the form of
snow-balls or snow-banks. It can result in vitreous
degeneration or posterior vitreous detachment.
Cataracts, especially the posterior sub-capsular
variant, cystoid macular edema and in extreme cases,
retinal neo-vascularization can occur.
Vogt - Koyanagi Syndrome
Management includes local steroids, ocular injectable
steroids and systemic steroids. In recalcitrant cases
immunosuppressive medications may be required .
Vogt-Koyanagi-Harada (VKH) disease is a multisystem
disorder characterized by granulamatous panuveitis
with exudative retinal detachment that is often
associated with neurologic and cutaneous
manifestations like poliosis, canities or vitiligo and
neurological (meningo-encephalitis) disorders. It is
treated with steroids and other immunosuppressive
medications.
Birdshot Retino Choroidopathy
Autoimmune Retinopathy
It is also known as vitiliginous choroiditis it affects
females in the fourth to fifth decade of life. More than
90% of the patients are HLA-A29 positive. Symptoms
include painless, gradual blurring of vision, floaters and
loss of colour vision.
Clinical signs multiple
depigmented yellow-white patches which radiate from
the optic nerve and follow the larger choroidal vessels.
The term 'birdshot' is given because the pattern of the
lesions in the fundus is similar to the shotgun scatter of a
birdshot. Vitritis, optic disc edema and cystoid macular
edema may be present. Ocular and systemic
corticosteroids are used. It is usually a chronic disease
with multiple recurrences and long-term visual
prognosis is guarded.
Here, auto-antibodies directed at various retinal
components cause progressive vision loss. Three forms
of autoimmune retinopathy are known - cancer
associated retinopathy, melanoma associated
retinopathy and non neoplastic autoimmune
retinopathy. These patients present with rapid, painless
vision loss associated with photopsias and
photosensitivity. This can progress to pan-retinal
degeneration without pigment deposits.
Corticosteroids - decrease antibody titers and stabilize
vision.
They usually cannot reverse vision loss.
Plasmapheresis combined with steroids and
intravenous immunoglobulin are also tried in severe
cases. However treatment results have been very
disappointing.
Choroiditis
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2014 Volume 27 No.1
Auto Immune Diseases & Ocular Manifestations
with preservative free artificial tear substitutes.
Common complains of patient with dry eyes are pain,
itching, redness of eyes blurring of vision, foreign body
sensation and tearing episodes.
Dry Eyes
Most of autoimmune diseases are associated with
dryness of eyes and must be treated symptomatically
Auto Immune Diseases & Ocular Manifestations





Ocular Pemphigoid
Mooren's Ulcer
Peripheral Ulcerative Keratitis
Episcleritis
Scleritis




Birdshot Retino Choroidopathy
Vogt - Koyanagi Syndrome
Autoimmune Retinopathy
Dry Eyes
Don’t want to stay in the hospital too long !
2014 Volume 27 No.1
21
Autoimmune Diseases
of the Skin
Dr. Nina Madnani
Dermatology Department
Case History:
A 50 years old lady presented to the dermatology clinic
with a six- year history of episodic symptomatic
ulceration on the left buccal mucosa that would last for
a few weeks, flaring up at times of stress. Range of
motion of temporo-mantibular joint was limited by the
right buccal mucosal scarring. She also complained of
itchy violaceous rashes especially on the limbs. She was
on treatment for hypertension and hypothyroidism since
four years.
Intra-oral examination revealed multiple erosions and
white streaks on the gingival and buccal mucosa.
Pigmented areas were also found. There were
violaceous polygonal flat-topped papules on the limbs.
A clinical diagnosis of Lichen Planus was made and
under local anesthesia a mucosal biopsy was
performed, which was reported as "erosive lichen
planus." The patient was treated with topical steroids.
She was advised that local steroid injection could be
considered, in the future, if necessary clinically
Discussion
Many skin diseases have an underlying autoimmune
basis. In clinical practice, the commonest auto-immune
skin diseases seen are lichen planus, alopecia areata,
vitiligo, psoriasis, immune-bullous diseases, and
chronic urticaria.
syndrome. The Hepatitis C virus has been associated
with a significant risk of developing lichen planus.
Topical corticosteroids are useful in limited disease.
Antihistamines help to control the itch and tacrolimus is
an alternative to steroids. Systemic treatment options
include griseofulvin, metronidazole, acetretin,
corticosteroids or rarely cyclosporine.
Alopecia Areata
Alopecia areata is an organ-specific auto-immune
disorder postulated to be caused by an aberrant
interaction between T-lymphocytes and HLA-DR
antigens expressed by the keratinocytes of the hair
follicles. Genes dictate the onset and severity of the
disease. Children and young adults are commonly
affected with an incidence between 10-30%. The
individual develops asymptomatic coin shaped
patch(es) of hair loss in one or more areas of the scalp,
often first noticed by the hairdresser. The patches may
increase rapidly to involve the entire scalp (Alopecia
Totalis) or entire body (Alopecia Universalis). Other
autoimmune diseases like thyroid disease, vitiligo, and
inflammatory disease (Crohn's disease) may co-exist.
Treatment is with intra-lesional / topical steroids,
anthralin, tacrolimus, and/or topical 5% minoxidil
solution for limited disease. Extensive disease may
require topical immunotherapy, PUVA, or oral
corticosteroids / methotrexate / azathioprine.
Vitiligo
Lichen Planus
This is an autoimmune, papulosquamous disorder in
which cytotoxic T-cells cause premature apoptosis of
basal keratinocytes and destruction of basement
membrane. It affects all age groups and involves the
skin and mucous membranes. The skin lesions are
characterized by itchy, violaceous papules which heal
with intense post - inflammatory pigmentation. Oral
disease may have varied morphological presentations
but most patients complain of intolerance to spicy food.
Erosive disease can be very painful and has an
increased risk to malignant change, hence needs to be
identified and treated early. Similarly, vaginal
involvement may be seen, especially in older women,
isolated, or as part of the vulvo-vaginal gingival
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2014 Volume 27 No.1
This socially significant disease, is characterized by
depigmented patches distributed over the body,
occasionally in segmental or acral patterns. Vitiligo
appears to be associated with certain alleles of the
major histocompatibility complex (MHC) class II
antigens as well as with other autoimmunesusceptibility genes. The positive response to
immunosuppressive therapeutic agents emphasizes the
role of autoimmunity in the development of this
disorder. It is now considered a part of a broader
autoimmune disease diathesis with an association with
thyroid disease, alopecia areata, pernicious anemia,
lichen sclerosis etc. There is a melanocyte-specific
cytotoxic-T-cell immune reaction resulting in
Autoimmune Diseases of the Skin
melanocyte destruction. Treatment modalities aim to
generate pigment from melanin-containing
appendageal structures like the hair follicles and also
from the functioning epidermal melanocytes at the
periphery of the patches. The extent and activity of the
disease process dictates the type of treatment. All
measures are aimed to convert an "unstable" disease to
a "stable" one. Extensive disease may require oral
steroids, NB-UVB, azathioprine, or methotrexate.
Stable vitiligo can be treated with topical steroids,
tacrolimus, anthralin and sometimes even surgery (esp.
segmental variant). Lasers like the excimer laser, and
targeted light therapy are the other modalities for small
stable lesions.
Psoriasis
This is a chronic inflammatory skin disorder in which
immunologically activated clonal T-cells stimulate
basal cell proliferation in the epidermis. Typically, the
disease presents as plaques with silvery scales on the
bony prominences, but may involve the scalp, nails, or
the entire integument.
Patients have a strong
association with HLA-Cw 6, HLA-Bw16, HLA-B13 and
HLA-B17 and those with psoriatic arthritis, HLA-B27.
Traditionally described as a disorder involving skin and
joints, it is increasingly being identified as a systemic
inflammatory disease affecting other systems
particularly the cardiovascular system. Percentage of
body surface area involved (> 10%) dictates the use of
systemic drugs like methotraxate, cyclosporine or
acetretin. PUVA, PUVA-SOL or NB-UVB is important for
larger plaques. Topical treatments include high potency
corticosteroids, tar-based ointments, calcipotriol and
keratolytics. The importance of moisturizers can never
be overstated. Biologicials like infliximab and
etanercept are reserved for resistant cases, or those with
joint involvement.
Immuno-bullous Disorders
This genetically determined group of disorders is
characterized by circulating autoantibodies against cell
membrane components or cell adhesion molecules. As
a result, the skin splits at varying levels which gives the
clinical phenotype.
Pemphigus Vulgaris (target: inter-cellular cementing
substance) is seen in patients in their fifth decade, but
may rarely be seen in a much younger age group.
Circulating IgG antibodies are directed against cell
adhesion molecules, (desmogleins -Dsg1 and Dsg3)
within the epidermal keratinocytes resulting in their
separation. Patients present with fluid-filled blisters on
the body and mucous membranes which easily
rupture to leave behind large erosions. The disease
can be effectively controlled with high dose
corticosteroids and other immunosuppressants.
Treatment may continue for years to maintain the
disease in remission.
Bullous Pemphigoid (target: basement membrane)
presents with tense bullae. The disease does not
involve the mucous membranes and may not be as
disabling as pemphigus vulgaris. Tetracycline and
nicotinamide combination provide a good
alternative to corticosteroids in controlling the
disease. Potent topical corticosteroids are useful in
limited disease.
Dermatitis Herpetiformis (target: dermo-epidermal
junction) is associated with gluten sensitive
e n t e r o p a t h y. M u l t i p l e s m a l l v e s i c l e s a r e
characteristically grouped on elbows, knees and
buttocks. Severe itching is the hallmark of this disease
as is the dramatic response to dapsone. A gluten free
diet helps to reduced dapsone requirement if not
control the disease.
Linear IgA Bullous diseases (target: dermo-epidermal
junction) shows a bimodal peak. In children, the
disease may start at 2-3yrs of age and spontaneously
remit by the age of 13. The classical presentation is
described as string of pearls since the bullae are
arranged in a rosette or annular array. Dapsone helps
to control the disease. The adult form of the disease is
usually precipitated by drugs, most commonly
- vancomycin and lithium.
Para-neoplastic pemphigus was originally described
in patients presenting with oral erosions, and a
blistering disorder with an underlying
lymphoproliferative malignancy. The histopathology
was a combination of features overlapping between
lichen planus and pemphigus. Now, besides
lymphoproliferative malignancies, lung
malignancies, thymomas and sarcomas have seen to
be associated. The diagnosis is a combination of
clinical, histopathological, immunofluorescence
findings, and the detection of an underlying
malignancy. Patients demonstrate antibodies against
desmoglein 3 and plakin proteins.
Chronic Autoimmune Urticaria
Chronic Autoimmune Urticaria (target: Fc receptors on
mast cells, anti IgE antibodies) Around 50% of chronic
idiopathic urticaria has now been identified to be
autoimmune. Circulating IgG autoantibodies are
2014 Volume 27 No.1
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Autoimmune Diseases of the Skin
directed towards the FcἐRI
receptors which are
present on the mast cells or rarely against IgE
antibodies. Fusion results in degranulation of mast cells
which in turn releases histamine and vasodilatory
substances. A strong association with HLA-DR4 is seen
in this group. Although thyroid autoantibodies may be
positive, most of these patients may be clinically
euthyroid. An important way to identify such patients is
the Autologus Serum Skin Test (ASST).
When
antihistamines fail and patients are plagued with wheals
and itching, immunotherapy with systemic
corticosteroids, cyclosporine, or even plasmapheresis
may be the only recourse.
Vitiligo showing per-follicular re-pigmentation
Today, with new techniques of detecting autoimmunity,
more and more traditional skin diseases are emerging
as "autoimmune" diseases.
Autoimmune diseases of the skin
Lichen Planus
Alopecia Areata
Vitiligo
Psoriasis
Immuno-bullous Disorders
Alopecia areata on beard area
o
o
o
o
o
Pemphigus Vulgaris
Bullous Pemphigoid
Dermatitis Herpetiformis
Linear IgA Bullous diseases
Paraneoplastic Pemphigus
Chronic Autoimmune Urticaria
Polygonal violaceous papules of lichen planus
24
2014 Volume 27 No.1
Adverse Effects of
Immunosuppressive Therapy
Dr. Gurmeet Mangat
Rheumatology Department
Although efficacious the various immunosuppressive
agents have varied and important side- effects that one
should be aware of while using them. This article
highlights the important side- effects.
Corticosteroids
These are often the back bone of immunosuppressive
therapy in various disorders. By nature steroids nonspecifically suppress various arms of the immune
system. The common side effects include weight gain,
fluid retention, glucose intolerance and hypertension.
However prolonged therapy also brings about a few
important adverse effects like skin thinning, cushingoid
features, osteoporosis, cataract and susceptibility to
infections.
Hydroxychloroquine (HCQ)
HCQ is a mild immunosuppressive agent which acts on
the immune system at an early stage of antigen
presentation. It is used in rheumatoid arthritis and
systemic lupus erythematosus. Common side-effects
include itching and skin pigmentation on prolonged
use. Rarely, it can cause pigmentary retinopathy. Hence
all patients on hydroxychloroquine should have their
fundus checked at least once a year. Myopathy and
muscle weakness are the other extremely rare sideeffects that can occur with prolonged use.
Methotrexate (MTX)
MTX has become the backbone of therapy for many
auto-immune diseases especially rheumatoid arthritis.
Usual side-effects include abdominal pain, oral ulcers
and hair loss. These usually prevented to a large extent
by the concomitant usage of folic acid.
Occasional elevation of transaminases (even up to 3
times the upper limit) is not uncommon and only needs
temporary cessation of the drug. Persistent elevation of
transaminases of more than 2 times the upper limit (6
episodes of elevation when measured every 6 weekly)
usually necessitates stoppage of the drug. These
patients also may merit liver biopsy. As the drug gets
excreted by the kidney, its dosage should be reduced in
those with renal involvement.
Extremely rarely it causes hypersensitivity pneumonitis.
This usually presents sub-acutely (over a few weeks) with
fever, cough and progressive dyspnoea. In such cases
the drug needs to be stopped and patient started on
high dose steroids to prevent morbidity and at times
mortality.
Leflunomide (LEF)
LEF is a drug that is used mainly in rheumatoid arthritis
and psoriatic arthritis. Its adverse effects mirror those of
methotrexate. Liver and lung abnormalities, like that
with MTX, are known with LEF. Loss of weight and
peripheral neuropathy are other specific abnormalities
known with LEF.
Azathioprine (AZA)
AZA has been used in rheumatic diseases like lupus for
many decades. Apart from gastrointestinal side-effects
it can cause cytopenia. This cytopenia is usually
reversible once the drug is stopped. Rarely, it can cause
drug induced hepatitis. Thiopurine methyltransferase
(TPMT) is the main enzyme responsible for inactivating
toxic products of azathioprine (AZA) metabolism.
Patients with homozygous deficiency of this enzyme
have no enzyme activity and ideally should not be given
AZA as in them life threatening neutropenic sepsis
occurs. This enzyme defect thankfully, is very rare.
However, some recommend that all patients should be
tested for TPMT activity prior to starting AZA therapy.
Cyclophosphamide (CPM)
CPM is a powerful immunosuppressant which has
varied uses. It is generally reserved for organ
threatening or life-threatening situations in patients with
rheumatic diseases. It can be used in the oral or
parentral form. Nausea and vomiting is not uncommon
in the oral form. It can also cause leucopenia. Since its
breakdown product acrolein is caustic, CPM causes
haemorrhagic cystitis as acrolein dams up in the
bladder. Intravenous CPM is less toxic than the oral
formulation. Its tendency to cause cytopenia or
haemorrhagic cystitis is much less than the oral
formulations.
2014 Volume 27 No.1
25
Adverse Effects of Immunosuppressive Therapy
Cyclosporine
Rituximab, Tocilizumab are some of them.
This drug acts through the calmoudulin pathway and
affects the function of "T" cells. It is extensively used in
organ transplant. In rheumatology it is mainly used in
connective tissue diseases. Apart from gastro-intestinal
side effects, it can cause elevated transaminases. Dose
dependant hypertension and elevation of creatinine is
also seen. Long term treatment can cause significant
hirsuitism.
As a group they rarely cause major organ dysfunction as
their side effects. Infections are the most dreaded
complication since these agents suppress the immune
system significantly (especially TNF blockers). In India,
tuberculosis is an important worry and complication
especially when using TNF blockers.
Immunosuppressive Agents
Mycofenolate mofetil
This new immunosuppressant is widely used in
transplant setup and connective tissue diseases. The
commonest side effect is abdominal pain and loose
motions. It can also cause leucopenia.
Biological agents
Over the last decade target specific agents have been
developed and used in rheumatology. The first group of
drugs to be used was TNF-blockers (etanercept,
infliximab and adalimumab). Subsequent to this various
other biological agents have been produced.
National Accreditation Board for Hospital &
Health Providers
26
2014 Volume 27 No.1

Corticosteroids

Hydroxychloroquine (HCQ)

Methotrexate (MTX)

Leflunomide (LEF)

Azathioprine (AZA)

Cyclophosphamide (CPM)

Cyclosporine

Mycofenolate mofetil
National Accreditation Board for Testing & Calibration
Laboratories - Department of Laboratory Medicine
certificate: M -0620
Laboratory Tests In
Rheumatology
Dr. Rohini Samant, Dr.Taral Parikh
Rheumatology Department
What tests do you really need to order for a
patient?
inflammatory arthropathy or systemic rheumatic
disease.
 Look for clues on physical examination.
1. A patient with possible rheumatic disease
2. A patient with known rheumatic disease
Primarily by history and physical examination
 Increase your "pretest probability" by asking
questions
that support the diagnosis of
Following routine tests may reveal helpful
information in assessing a patient with possible
rheumatological condition.
 Anemia, other cytopenias - usually help
inassessing the disease activity and in monitoring
drug side effects. It is also necessary to be aware
of other causes of changes in these parameters.
Low Hemoglobin
Active rheumatoid arthritis (RA)
Dietary deficiency, autoimmune hemolytic anemia,
NSAID induced GI blood loss, Felty's syndrome, drug
induced marrow suppression, renal impairment
WBC abnormalities
Low in active SLE
High in infection and vasculitis
LOW: drug Induced marrow suppression, Felty's
syndrome
Eosinophilia
Systemic vasculitis
Drug reaction
Eosinophilia GPA,
Granulomatous PolyAngiitis (GPA),
PolyArteritis Nodosa
Platelet abnormalities
Both disease related and unrelated
Thrombocytosis: Fe Deficiency, active RA,
acute blood loss, vasculitis
HIGH: steroid therapy, acute arthritis, acute gouty
attack, Still's disease
Thrombocytopenia: Drug induced marrow
suppression, APLA, Felty's syndrome, SLE
ESR
Increased Acute phase reactants, anemia (fewer cells,
less repellent forces)
CRP
Direct measure of acute phase reactants.
Advantages - It is less sensitive to irrelevant factors like
age, gender and anemia, responds more quickly.
Disadvantages - More expensive, don't always know
how to interpret.
2014 Volume 27 No.1
27
Laboratory Tests In Rheumatology
Both ESR and CRP are not specific for any CTD, they
help in drawing the attention towards the systemic
inflammatory response versus a more benign condition.
In most of the diseases a decrease in these parameters
usually suggest a response to therapy.
symptoms suggestive of an underlying rheumatic
condition.
 Rheumatoid Factor (RF) - It is the most commonly
used screening test for diagnosis of inflammatory
polyarthritis (RA). It is positive in other conditions
like- MCTD, SLE, Scleroderma, Sjogren's
syndrome, Cryoglobulinaemia.
 Urinary abnormalities- like active urinary
sediment helps in diagnosing renal
involvement in conditions like SLE and systemic
vasculitis.
 Elevated serum creatinine is a marker for
diagnosing rapidly progressive cresentric GN
and underlies the need for a more intensive
therapy I
ncluding kidney biopsy.
 CPK elevations are associated inflammatory
myositis.
 High globulins suggest an active disease and a
chronic inflammatory state.
 Liver function tests helps in detecting the liver
involvement in various diseases and in
monitoring side effects of
immunosuppressant
therapy.
 Thyroid function tests should be ordered as it is a
common cause for various musculoskeletal
complaints and its prompt treatment alleviates
many of these complaints.
 Vitamin D3: If the patient is affording this test
should be ordered. Vitamin D3 supplements may
be given without testing if the patient is not
affording as in India Vitamin D3 deficiency is very
common, more so in rheumatic diseases.
 Chest X ray as a part of routine investigation is
helpful not only for diagnosing underlying ILD in
various CTDs but also in ruling out infections
such as tuberculosis.
It is positive in 75% of RA patients and
associated with extra articular manifestations. But in
may be present in 15% of population > 65
years of
age.
Non rheumatological conditions with RF positive
o
o
o
o
Viral infections - Hepatitis C
Parasitic infections - Kala Azar
Chronic bacterial infections - T.B, Hansen's
Neoplasm
Rheumatoid factor is not diagnostic for
rheumatoid arthritis. The test's utility is greatest
when there is a moderate pre-test probability of
the disease.
Common Immunological Tests
Screening Tests
These tests are ordered when a patient has history and
 Anti-CCP antibody - it is newer test for
diagnosing RA. It is an antibody directed against
"citrullinated" peptide residues present
within inflammatory sites. It has a sensitivity
equivalent to RF and greater specificity than IgM
RF. It is part of the new 2010 ACR guidelines for
diagnosis of RA. It may be detected in healthy
people years before onset of RA.
 ANA (Anti nuclear antibody) - It is the most
important screening test for a connective tissue
disorder (CTD), like SLE in a patient presenting
with features like fever, hair loss, photosensitive
rash, mouth ulcers and arthritis. Its absence virtually
excludes SLE and it is positive in 95% of
S L E
cases.
It is also positive in other CTDs like Scleroderma
and Sjogren's syndrome.
Non - rheumatological conditions with positive ANA
Malignancies:
lymphoma,
leukemia,
melanoma, solid
tumors
(ovary, breast,
lung, kidney)
Normal individuals: females > males, increasing age, relatives of patients with rheumatic
disease, pregnancy
Autoimmune thyroiditis, Type 1 Diabetes Mellitus
Hepatic diseases e.g. chronic active hepatitis
Pulmonary diseases e.g. idiopathic pulmonary fibrosis
Chronic infections
Hematologic disorders: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia
Drug- induced: hydralazine, phenytoin
28
2014 Volume 27 No.1
Laboratory Tests In Rheumatology
So, when should I order an ANA?
is important to keep in mind the clinical profile of
patient with gout- monoarticular, acute involvement of
MTP joint typical of gout, but acute knee, ankle or
polyarticular involvement may occur.
Asymptomatic hyperuricemia is a common component
of the metabolic syndrome and only a small proportion
of patients with asymptomatic hyperuricemia will
develop gout. It is important to know that the incidence
of gout increases as the severity and duration of
hyperuricemia increases.
Synovial fluid analysis
It is important for diagnosing infectious arthritis,
crystallopathies like gout and CPPD (Calcium Pyro
Phosphate Deposition) and monoarthritis.
Infections usually cause a synovial fluid WBC count >
50,000 c/mm3, inflammatory arthritis and
crystallopathies WBC count between 5,000-50,000
c/mm3 and non inflammatory conditions like OA have
a WBC count < 500/mm3.
Imaging Techniques in Rheumatology
a)Plain X-ray hands with wrists help in diagnosing
various conditions like RA, SpA, gout and assessing the
presence of damage like erosions and joint space
narrowing.
o Perinuclear staining - P-ANCA
o Cytoplasmic staining -C-ANCA
Plain X-ray SI joint for diagnosing SpA like AS, PsA and xray lumbar and cervical spine for involvement in RA and
SpA.
b) CT scan and MRI
ANCA most strongly associated with necrotizing
vasculitis
C-ANCA (Pr3)  Wegener's granulomatosis /
Granulomatous polyangitis
P-ANCA (MPO)  Microscopic polyangitis, ChurgStrauss vasculitis
But it is not required to confirm a clinical and radiologic
diagnosis of Ankylosing spondylitis (AS). Its sensitivity is
95% for patients with Ankylosing spondylitis, 70% with
reactive arthritis, and 60% with Psoriatic spondylitis
(PSA).
c) Ultrasound is gaining popularity for diagnosing
inflammatory arthritis, shoulder disorders and for joint
aspiration and injection.
It is important to keep in mind that it is present in 5-8%
general population. HLA B27 of no value in diagnosing
usual patient with back pain.
d) Radioisotope scanning is not ordered as a routine test
and in unusual situations it is helpful in picking up an
occult inflammatory arthritis or infection.
Uric acid
 Tests for extra articular manifestations
It is a commonly abused test. Before ordering this test it
2014 Volume 27 No.1
29
Laboratory Tests In Rheumatology
These tests are important for assessing the systemic
involvement in CTD like the lungs, heart, kidney and
Role Following
of CT Scanare some of theseEarly
brain.
tests: diagnosis of
sacroilitis,
vertebral
X-ray Chest (effusion, nodules, infections), PFTdisease
(DLCO),
and
d e sinvolvement.
truction,
CT-Chest
(HRCT), BAL: for pulmonary
subchondral
fractures
CSF, MRI, and CT-Brain: for CNS involvement.
Role of MRI scan
Most sensitive for avascular
2 D Echo for PAH and cardiac
involvement
in CTDs.
necrosis,
craniocervical
region
in RA, SpA, direct
Barium Studies, OGD scopy
- Scleroderma
visualization of
articular
EMG, nerve Conduction- in peripheral cartilage
neuropathies
and myositis.
Bone Densitometry - DEXA, T Score, Z score;
osteoporosis.
Other tests
HBsAg, Anti HCV, TSH, lipid profile, serum
electrophoresis, VDRL, HIV, Hb electrophoresis,
cryoglobulins, immunoglobulins, anti phospholipid
antibodies dictated by the patients history and
30
2014 Volume 27 No.1
background illness.
On the trail of diseases, years
before they strike - Auto antibodies
Dr. Vipla Puri
RIA Laboratory Department
Auto antibodies are the markers of future disease in
presently healthy individuals. Although auto antibodies
might not always be directly responsible for many of the
manifestations of auto immune diseases, but assaying
auto antibodies for prediction of disease could lead to
intervention trials to prevent auto immune organ
specific diseases like Type 1 Diabetes, Thyroid disease,
Myasthenia gravis or systemic illnesses like Rheumatoid
Arthritis (RA) and Systemic Lupus Erythematosus
(SLE).Thus predictive auto antibodies are molecules
that appear in blood years before people show
symptoms of various disorders. Tests that detect these
molecules could warn of the need to take preventive
action.
Auto Antibodies as Markers of Disease Activity,
Severity and Classification
Antibodies may reflect the presence, nature and
intensity of immune response. Since in auto immune
diseases the immune response is itself part of the
disease process, it is possible to use auto antibodies as
markers of disease activity. These auto antibodies can
be detected in certain diseases with a long prodrome
during which there are no clinical symptoms. The titer or
the levels of these auto antibodies can also predict both
the likehood of clinical disease and rate of progression
of the disease i.e. the disease activity and the severity of
the disease.
Many auto immune diseases are chronic condition that
progress over the course of time and are characterized
by the presence of auto antibodies that precede the
overt disease by months or years. It is now known that
the presence of two, Islet cell Antibodies (ICA) are
associated with a 50% risk of developing diabetes
mellitus in 5 years, Anti Cyclic Citrullinated Peptide
(Anti-CCP) antibodies are found in sera of Rheumatoid
arthritis patients 4 to 5 years before the overt disease,
and in SLE patients accrue antibodies throughout a
foreseen course during 3 - 4 years before the clinical
symptoms.
The introduction of tests recognising Anti CCP
antibodies has revolutionised practice in
Rheumatology. These antibodies have recently
emerged as sensitive and specific serological markers
of Rheumatoid Arthritis (RA), providing an additional
and superior marker of rheumatoid factor. The first
members of this autoantibody family were antiperinuclear factor and anti-keratin antibodies both of
these recognise citrullinated epitopes of flaggrin.
Citrullination is a post translational modification of
arginine by deimination, physiologically occurring
during apotosis, inflammation or keratinization. The
presence of several citrullinated proteins has been
demonstrated in RA synovium. The identification of
citrullinated epitopes as targets for antiflaggrin
antibodies led to the development of first and later
second generation anti-cyclic citrullinated peptide
antibody assay.
With the availability of sensitive and specific assays, Anti
- CCP antibodies has become a "Key" serologic marker
in RA and is considered a potential surrogate marker for
diagnosis and prognosis of rheumatoid arthritis. It is
now included in the classification and diagnostic
criteria of American College of Rheumatology.
a) Since it is more specific than IgM rheumatoid
factor (RF)in early and fully established disease
b) Can predict eventual development into RA when
detected in undifferentiated arthritis.
c) A marker of erosive disease in RA.
d) May be detected in healthy individuals' years
before the onset of clinical RA.
It remains to be seen whether the use of Anti - CCP
antibodies will allow the clinical rheumatologist to
better predict the diagnosis and prognosis of individual
patients and help in more rational therapeutic decision
making thus influencing the long term outcome of the
disease. Although screening of populations for
susceptibility to certain autoimmune diseases is now
feasible, high throughput, cost effective methods
should be available to detect individuals at high risk for
a specific autoimmune disease. The practical value of
screening will be enhanced once preventive measures
and safe therapy become available.
2014 Volume 27 No.1
31
Rheumatology Quiz
Dr. C. Balakrishnan
Q1 : 40 yrs old male with back pain of
10 years duration
Q 3: A 60 years old man with painful
right lower limb
What is your diagnosis?
What test will prove it?
What is the diagnosis?
What other tests will you do?
What is the treatment of choice?
Q 2: A 12 years old boy with pain in
the legs
Q 4: 43 years old male with easy
fractures
What does the plain x-ray show?
What is most likely disease?
What is the diagnosis?
Q1: 1) Alkaptonuria
2) Urinary homogentisic acid
Q2: 1) Subcutaneous calcification
2) Dermatomyositis
Q3: 1) Paget’s disease of the tibia
2) serum alkaline phosphatase, urinary collagen cross links, bone scan
3) If active: Bisphosphonates
Q4: Interrosseous membrane calcification due to fluorosis.
2014 Volume 27 No.1
Answers
32
Our Team
Rheumatology Faculty
Dr. V. R. Joshi
Dr. C. Balakrishnan
M.D., FRCP
Consultant Physician & Rheumatologist
Director, Research
MD
Consultant Rheumatologist
Dr. Rohini Samant
Dr. Gurmeet Mangat
MD
Consultant Rheumatologist
MD
Consultant Rheumatologist
2014 Volume 27 No.1
33
P. D. Hinduja Hospital & Medical
Research Centre - News
P. D. Hinduja Hospital retains position of the Best Multi-Specialty
Hospital in Mumbai
Title bestowed at the first edition of Healthcare Achievers Awards 2014
From Left to Right: Mr. Joy Chakraborthy, Director - Times Group,
Mr. Gautam Khanna, CEO-P.D. Hinduja Hospital & MRC, Mrs. Usha Raheja,
Trustee-P.D. Hinduja Hospital & MRC, Shri Ram Vilas Paswan, Union Food and
Consumer Affairs Minister, Mr. Luv Verma, Secretary-Dept. of Health and
Family Welfare, Mr. Joy Chakraborty, COO-P. D. Hinduja Hospital & MRC,
Mr. G. Srinivas, CMD-The New India Assurance Co. Ltd, Dr. Sanjay Agarwala,
Director-Professional Services, - P. D. Hinduja Hospital & MRC
P. D. Hinduja National Hospital & Medical
Research Center, Mumbai continues this year's
award-winning streak with the prestigious title of
the 'Best Multi-Speciality Hospital-Mumbai' (surveybased category) awarded at the Healthcare
Achievers Award 2014, presented by New India
Assurance Co. Ltd. and The Times of India on 11th
December 2014 in New Delhi. In its first year, the
awards have been instituted to honour excellence
in the Healthcare Sector across single speciality,
multi-speciality and secondary care hospitals, who
have contributed in helping India emerge as one of
world class destinations in healthcare. This
recognition re-affirms Hinduja Hospital's position
asa pioneer and leader in health care delivery in the
country.
In an evening that celebrated excellence in
Healthcare, P. D. Hinduja Hospital was recognized
as the healthcare provider who raised the bar for this industry with its dynamic spirit and innovative outlook thereby
helping people lead quality lives. The award was presented by Union Food and Consumer Affairs Minister, Ram Vilas
Paswan to the hospital Trustee Mrs. Usha Raheja, along with Mr. Gautam Khanna, CEO,
Mr. Joy Chakraborty, COO and Dr. Sanjay Agarwala -Director of Professional Services, of
P. D. Hinduja Hospital, at the event that witnessed leaders from across the pharmaceutical
and healthcare industry. Shri G. Srinivasan, Chairman & Managing Director of The New
India Assurance Co. Ltd, Mr. Luv Verma, Secretary-Dept. of Health and Family Welfare and
Mr. Joy Chakraborthy, Director Times Of India group were among the dignitaries present at
the event.
The consistent recognition gained by P. D. Hinduja Hospital this year, showcases the trust
shown by patients and communities in the core values of the institute and the quality of care
provided by the hospital. Speaking on the occasion, Managing Trustee Ms. Vinoo S.
Hinduja said, "We have always stood by our mission of 'Quality Healthcare' with a strong
sense of purpose laid by the founder of the hospital, Sri Parmanand Hinduja, to serve our
patients. The consistency, with which P. D. Hinduja Hospital has been recognized as one of
the country's best hospitals, reflects the growth, hard work and dedication to patientcentered care and excellence that is embedded in our legacy. Through innovative
technology, accreditation and knowledge driven employees, our hospital has been 'Best Multi-Speciality HospitalMumbai' (survey-based category)
relentless in its pursuit of excellence."
The winners of the 'Best Multi-Speciality Hospital in Mumbai' - at the first edition of
Healthcare Achievers Awards 2014, were determined through a research
34
2014 Volume 27 No.1
awarded at the Healthcare Achievers
Award 2014, presented by New India
Assurance Co. Ltd. and The Times of
India
P. D. Hinduja News
Contd.
methodology based on factual information obtained from numerous short listed hospitals across India. The survey
included feedback from the doctor community towards understanding the hospitals in their consideration and
preference list. Patients evaluated the hospitals based on behavioral and emotive loyalty besides their performance
based on "Compassionate patient care", "Patient safety" and "Customer excellence"
"We are extremely proud and honored that our continued dedication and passion for providing high quality care to
each and every one of our patients was recognized by these prestigious awards. We are constantly investing in
technology and talent to ensure we operate to the highest possible standard and continually provide newer solutions
and care for patients." said Mr. Gautam Khanna, Chief Executive Officer, P. D. Hinduja Hospital.
P. D. Hinduja Hospital has provided more than six decades of selfless and dedicated service of providing ethical, value
based quality healthcare for the people of India. The hospital has recently received various industry awards for
healthcare delivery, innovation and technology. The institution's focus has always been to provide a patient centric
healthcare experience that allows access to the best doctors and technology at an affordable cost.
P. D. Hinduja Hospital & Medical Research Centre to cement an Innovation Lab
P. D. Hinduja Hospital, IIT-Bombay, WeSchool come together to create a platform
for innovation for the youth of India
th
On occasion of the 65 Republic Day of India when India looks at becoming a young superpower, this event created a
platform for innovation and opportunity for the youth of India. The event is the beginning of a week-long workshop
being held at IIT Bombay and at WeSchool with MIT delegates.
During this event, doctors from P. D. Hinduja Hospital presented their innovative ideas and expectations to the young
and entrepreneurial students from IIT-B, WeSchool and MIT.
Inspired by the doctors wish list, P. D. Hinduja Hospital's Executive Trustee Ms. Vinoo Hinduja announced an
"Innovation Lab" where the youth of India would come together to develop economical medical and diagnostics
equipments/facilities for the people of India. This Innovation Lab will be 'By India, Of India and For India' and Indian
institutes like IIT-B and WeSchool will join hands with P. D. Hinduja Hospital to create this platform with MIT being
facilitator in this innovation. P. D. Hinduja Hospital looks forward to many more collaborations with domestic and
international institutes for its innovation lab.
26th January, 2014 workshop
2014 Volume 27 No.1
35
P. D. Hinduja News
Contd.
Announcing the new innovation lab, Ms. Vinoo Hinduja said, "The deficiencies in healthcare industry are a fertile land
waiting for the youth of India to plant it seeds of innovation to reap the fruits of success. I urge you all to embrace
transformation so as to be able to address some of patient care issues."
Mr. Joy Chakraborty, COO, P. D. Hinduja Hospital said, "India needs innovation to make healthcare accessible and
affordable. Our endeavor is a small step towards the need of the health sector. One of our principles 'Partnership for
Growth' is followed in different ways in our practices and this Innovation Lab will stand for a partnership with credible
and similar minded partners across the globe to achieve our objectives."
Dr. Sanjay Agarwala, Director - Professional Services said, "This is a forum where all participating students from IIT,
MIT etc could interact with doctors of Hinduja Hospital so that they could innovate and find solutions through ideation,
leading to a product that would help the same doctors across the world in diagnosis."
The P. D. Hinduja Hospital has always been in the forefront of technology. Dr. Camilla Rodrigues, Consultant
Microbiologist & Chairperson Infection Control Committee said, "One of the thrust areas has been in tuberculosis
diagnostics. The hospital is well known as a pioneer in this field. The Govt of India has recently recognized our lab for
second line testing of drug resistant tuberculosis. This innovation lab initiative that will also focus on TB is certainly a
step in the right direction to the laudable goal of a TB free India.”
P. D. Hinduja Research Centre and Hospital celebrated Republic Day by felicitating
50+ Organ Donors to spread awareness for Organ Donation on 26th January, 2014
~Film maker Madhur Bhandarkar aralong with Director Karan Malhotra, Actor Darshan Jariwala & well
known Comedian Manoj Joshi were a part of the awareness programme at the hospital~
~Cardiac patient father who donated kidney to daughter suffering from Juvenile Diabetes, Donor from Nagaland
amongst others were felicitated~
Pioneering healthcare provider-P. D. Hinduja Hospital has pulled out all the stops to take healthcare a step further by
th
felicitating the heroic act of organ donation. In its 7 edition, the organ donor felicitation endeavour anchored by the
hospital aims at honouring & encouraging donors from various walks of life for their noble act. National Awardwinning film maker Madhur Bhandarkar along with new age Director Karan Malhotra (of Agneepath fame),
National Award winning actor Darshan Jariwala
and well known character artist & comedian Manoj
Joshi were seen applauding the spirit of 50+
national & international donors who were
felicitated on the occasion of Republic Day at
Hinduja Hospital.
Speaking on the occasion Dr. Alan Almeida,
Section Co-ordinator, Nephrology says, 'For
organ recipients, a transplant often means a second
chance at life & allows many recipients to return to a
normal lifestyle. We at Hinduja Hospital strongly
advocate the cause of organ donation and ensure
the process is fruitful for each recipient. Our efforts
are concentrated to bridge the demand supply gap
of organs in the country as about 5,00,000 people
die to non-availability of organs every year’
36
2014 Volume 27 No.1
Dr. M. Kamath & Film maker Madhur Bhandarkar applauding the spirit
of the donors at the Organ Donation Felicitation
programme by Hinduja Hospital
P. D. Hinduja News
P. D. Hinduja Research Centre and Hospital's Allied Health Sciences Courses gets
HSSC affiliation
The Allied Health Sciences Courses which got off to a flying start since its launch in 2012 has now received an
affiliation from the Health Sector Skills Council (HSSC), a not-for-profit organization, registered under the Societies
Registration Act, 1860. The affiliation from the council makes Hinduja Hospital the only hospital in the country to have
been certified to conduct these allied courses under pilot phase of Star Scheme of Government of India. The council
has been promoted by Confederation of Indian Industry (CII) and leading Healthcare Industry Members representing
both public and private sector, constituted and financially supported by National Skills Development Corporation
(NSDC a pioneering PPP set up under the aegis of Ministry of Finance). P. D. Hinduja Hospital will be conducting
courses in 4 primary departments namely Radiology, Dialysis, Medical Laboratory and Operation Theater.
The courses are being conducted in 2 formats: Part-time & Full time. The Part-time course begins from January and
caters to the practicing professionals who are HSC pass and have experience in the field. Duration of course is 7months, with once a week lectures. The same courses are also available as full time with duration of 1 year, catering to
freshers, whose batches will start in August 2014. Other full time courses (non-affiliated) from the Allied Health
Sciences stable are MRD Technician, CSSD Technician and Physician office assistant courses. These courses will be
beneficial to the students by giving them the opportunity to get certified under government scheme along with enjoying
get monetary reward on certification.
P. D. Hinduja Hospital adjudged as “Best Multi-Speciality Hospital of the
Year” at e-Health Maharashtra Awards 2014
P. D. Hinduja Hospital & Medical Research Centre,
established in 1951, a leading tertiary care hospital in India,
has been adjudged as the 'Best Multi Specialty Hospital of
The year' at the e-Health Maharashtra Healthcare
Leadership Awards & Summit held on July 11, 2014. At a
glittering ceremony held at The Courtyard Marriott, Pune,
Mrs. Meeta Rajiv Lochan, Secretary, Department of Public
Health, Govt. of Maharashtra presented the award. Mr. Joy
Chakraborty, COO, P. D. Hinduja Hospital received the
award on behalf of the Hospital.
Mr. Gautam Khanna, CEO, P. D. Hinduja Hospital said, “We
feel proud to be adjudged as the best multi specialty hospital
and to have received this prestigious award. It was our
Founder, Sri. P. D. Hinduja's vision to build a world-class, affordable hospital to provide Quality Healthcare for all at
par with international standards. The dream was then later carried forward to reality by Late Smt. Lalita G. Hinduja,
Sri. P. D. Hinduja's eldest daughter-in-law, who spent 30 years nurturing this vision. She created a culture of
compassion and care amongst the employees, weaving them into a family. Mr. Khanna added, “It is the patient
centricity and parivaar values at the Hospital which make employees go beyond the call of duty to deliver high quality,
affordable, personalized care to all patients.”
Mr. Joy Chakraborty, COO, P. D. Hinduja Hospital on receiving the award said, "We are extremely delighted to have
received this award. The recognition is a result of the commitment of every individual working with the hospital in
giving the best patient care. This award will be a great motivation for the staff at the hospital.” He attributed the
achievement to the strong sense of purpose laid by the Founder of the Hospital, Sri Parmanand Hinduja, to serve the
community.
The hospital had won the e-Maharashtra award for the 'Best ICT enabled hospital' in 2013. The current award in 2014
is another stepping stone in the relentless pursuit of excellence for the Hospital.
2014 Volume 27 No.1
37
Welcome to
P. D. Hinduja Hospital Pariwar
Dr. Aman Daftary
Imaging (Mammography
and Breast MRI)
MBBS, DMRD
Dr. Ganesh Nagarajan
Gastroenterology Surgery
(Oncology)
M.S, FCPS,
Fellowship HPB & Liver Transplant
(France)
Dr. Neelu Desai
Pediatric Neurology
MD (Ped), DNB, Bill Marshall
Fellowship (UK),
Fellowship in Pediatric Neurology
(London)
Dr. Lancelot Pinto
Pulmonology
MBBS, DNB (Respiratory Medicine),
MSc (Epidemiology - McGill
University, Canada),
Fellow (Sleep medicine and COPD
Rehabilitation McGill University, Canada),
FCCP (USA)
Dr. Nilesh Doctor
Gastroenterology
Visiting Consultant
MBBS and FRCS
Dr. Ameet Mandot
Gastroenterology
Visiting Consultant
MBBS, MD, DNB (Gastro)
38
2014 Volume 27 No.1
Dr. Purushottam Kand
Nuclear Medicine
M.B.,B.S.(Mum),
D.R.M.(Mum),
D.N.B.(Nucl. Med.), M.N.A.M.S.,
Diplomate C.B.N.C.(USA)
Fellow, European Board of
Nuclear Medicine
Dr. B. Satyanand Shastri
Pulmonology
MBBs, MS,
FRCS.
Dr. Raashi Khatri Panjabi
MD (USA), BDS
Visiting Consultant in Orofacial
Pain Management including
Temperomandibular Disorder, Post
Cancer Jaw Stabilization, and
Musculoskeletal pain &
Neuropathies of head & neck
Spreading health & happiness
as we move ahead!
,
by Doc N Doc ‐ Gammex Saviour Awards. We believe it is your faith in us that has been our biggest motivation in being the best!
Awarded