Download Connective Tissue Diseases Adam Wray, D.O. September 7, 2004

Connective Tissue Diseases
Adam Wray, D.O.
September 7, 2004
ANA Assay
 Classic ANA immunofluorescence is still considered first
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line screening test for AI-CTD
Historically, rodent cells rather than human cells were used
as the substrate
Rodent cell nuclei lack some autoantigens present in
human cell nuclei (Ro antigen)
1-2% of SLE patients are ANA (-) using human tumor cell
line base substrate (Hep-2)
Hence, “ANA negative SLE” a historical phenomenon
Titer of <1:160 using human tumor cell line substrate has
little clinical utility
ANA Immunofluorescence Patterns
Drug Induced ANA/SLE
 Procainamide
 Hydralazine
 Isoniazid
 Chlorpromazine
 Phenytoin
 Methyldopa
 Minocycline
Lupus Erythematosus
 Chronic Cutaneous LE
– DLE
– Verrucous LE
– Lichen Planus-LE overlap.
– Chiblain LE
– Lupus Panniculitis (LE profundus)
• With DLE
• With Systemic LE
Discoid LE
 Young adults. F:M=2:1
 Cat’s Tongue (Langue au chat) = carpet
tacks
 Lesions heal centrally first with atrophy,
scarring, and dyspigmentation
 Up to 24% will have mucosal involvement.
 95% of cases confined to the skin at the
onset and will remain so.
Discoid LE
 Unusual for lesions below neck without
lesions above the neck
 Spontaneous involution with scarring is
common
 Progression to SLE is rare and may be
identified by abnormal labs.
– ANA – elevated
– Leukopenia, hematuria, or albuminuria
Histology
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Thinned epidermis
Loss of normal rete ridges
Follicular plugging
Hydropic changes of basal layer
Lymphocytic perivascular infiltrate
Increase interstitial mucin depositon
Pilosebaceous atrophy discriminates from SCLE
DIF is positive more than 75% of cases with Igs
located at DEJ
Treatment
 SUNSCREEN!!!!
 Topical steroid, high potency with occlusion if
needed.
 Intralesional Injection with Kenalog
 Antimalarials: safest and most beneficial system
therapy.
– Plaquenil for 3 months, if no response switch to Aralen.
– If response is still incomplete, add Quinacrine, since
this won’t increase retinal toxicity
Verrucous LE
 AKA hypertrophic LE
 Resembling KA or hypertrophic LP
 Treatment with TAC or Intralesional
 Also can be treated with Accutane or
Plaquenil.
Verrucous LE
 2% of patients with
chronic cutaneous LE
 Histo: epidermis is
papillomatous,
hyperplastic, and
surmounted by
hyperkeratotic scale
LE-LP Overlap syndrome
 Large atrophic hypopigmented bluish-red
patches and plaques.
 Fine telangiectasia and scale usually present
 Response to treatment is poor
 Dapsone or Accutane maybe effective
Chilblain LE
 AKA lupus pernio
 Chronic, unrelenting form of LE with
fingertips, rims of ear, calves and heels in
women.
 Chilblain lesions are due to cold
 Usual LE treatment
LE Panniculitis
 AKA LE Profundus
 Deep subcutaneous nodules 1-4cm
 Head, face, and upper arms
 Woman age 20-45
 Histology shows lymphocytic panniculitis, hyaline
degeneration of the fat, hyaline papillary bodies.
Over lying epidermis shows hydropic changes and
follicular plugging
 Treatment with Antimalarials.
SCLE
 Subacute cutaneous LE
– Papulosquamous
– Annular
– Syndromes commonly exhibiting similar
morphology
• Neonatal LE
• Complement deficiency syndromes
SCLE
 Typically
photosensitive
 Lesions confined to
sun-exposed skin
 Regular association
with anti-Ro antibody
(SS-A)
SCLE
 Psoriasiform, polycyclic annular lesions
 Shawl distribution: V neck, upper outer and
inner arms.
 ¾ of the patients have arthralgia
 20% have leukopenia
 80% have positive ANA
 Associated with HLA-DR3-Positive.
Drugs triggering anti-Ro antibodies
and thus lesions of SCLE
 HCTZ
 NSAIDS
 Diltiazem
 Griseofulvin
 Terbinafine
 Lesions may or may
not clear once the
medication is
discontinued.
Neonatal LE
 Annular scaling erythematous macules and
plaques
 Appear on head and extremities
 First few months of life in babies born to
mothers with LE, RA, or other connective
tissue disease
 Resolve spontaneously by 6 month of age
 HALF of the patients have associated
congenital heart block, usually 3rd degree
Neonatal LE
 Lesions histologically identical to SCLE
 Almost 100% have anti-Ro antibodies
 Unlike adult SCLE, lesions have
predilection for the face, especially
periorbital region
 Lesions typically resolve without scarring
 Other internal findings
– Hepatobiliary disease
– Thrombocytopenia
Acute Cutaneous LE
 Characteristic butterfly facial erythema
 May last from days to several weeks
 Bullous lesion occur as single or grouped vesicle
or bullae
 Subepidermal bulla containing neutrophils.
 HLA-DR2 positive
 Minute telangiectasias appear in time on the face
or elsewhere and commonly appear about the nail
folds.
 Rowell Syndrome: EM-like lesion dominant in LE
Systemic LE
 Young to middle age women
 Skin involvement occur 80% of the case
 American Rheumatism Association has 11
criteria
 If 4 or more of the criteria are satisfied, the
patient is said to have SLE
ARA SLE criteria
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Malar Erythema
Discoid Lupus
Photosensitivity
Oral Ulcers
Arthritis
Serositis
Nephritis
Hematologic
CNS Changes
Immunologic disorder
ANA
Systemic Manifestation.
 Arthralgia is the earliest abnormality.
 95% of SLE patient will have arthralgia.
 Avascular necrosis of femoral head.
 Thrombosis in vessels secondaary to
presence of lupus anticoagulant.
 Renal involvement in nephritic or nephrotic
type.
 Mycocarditis, cardiomegly, EKG changes.
Systemic Manifestation.
 CNS involvement
 Idiopathic thrombocytopenic purpura.
 Sjogren’s syndrome
 Mixed with dermatomyositis
Treatment of SLE
 Treatment depending on the organ system(s) involved.
 Skin, musculoskeletal, and serositis-type manifestations
generally respond to treatment with hydroxychloroquine
and nonsteroidal anti-inflammatory medications.
 Porphyria cutaneous tarda may co-exist with LE, in this
case, Plaquenil is TOXIC!!!
 More serious organ involvement, such as CNS
involvement or renal disease, often necessitates
immunosuppression with high-dose steroids and
cyclophosphamide.
 Stop smoking!
Dermatomyositis
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Poikiloderma
Gratton's sign - flat-topped violaceous papules
Heliotrope - reddish -purple flush around the eyes
Over knuckle streak erythema
Shawl pattern
Bimodal distribution
Calcinosis Cutis may occur in over half of the
children with DM
 Associated with Malignancy in 10-50% of adults
Dermatomyositis
 Symmetrical muscle weakness
 assoc c malignant neoplasm when over 40
 periungual telangiectasia
 Prednisone 1mg/kg with slow taper
 Sunscreen, antimalarial
 Mechanics hand: hyperkeratosis, fissuring,
scaling involvement in the palm of the
hand.
Muscle involvement
 Symmetrical muscle weakness
 Unable to raise arms to comb their hair
 Cardiac involvement with cardiac failure in
terminal phase
 Amyopathic dermatomyositis or
dermatomyositis sine myositis: DM without
muscle changes
Childhood DM
 Brunsting type
– Slow course
– Progressive weakness
– Calcinosis
– Steroid responsiveness
 Banker type
– Vasculitis of muscles
and GI tract
– Rapid onset
– Severe weakness
– Steroid
unresponsiveness
Scleroderma
 characterized by symmetric thickening,
tightening, and induration of the skin of the
fingers and the skin
 These changes may affect the entire
extremity, face, neck, and trunk (thorax and
abdomen).
 Occurs in localized and systemic forms
Localized Morphea
 Smooth, hard, somewhat depressed,
yellowish white, or ivory-colored lesions.
 Common on the trunk
 Margins surrounded by light violaceous
zone or by telangiectasias.
 Resemble pigskin (prominent follicular
orifices)
 Slowly involute over a 3-5 year period.
Generalized Morphea
 Widespread hard indurated plaques.
 No systemic involvement
 Patient appear young because of the
firmness of the skin.
 Resolution less likely than the localized
version.
Atrophoderma of Pasani and Pierini
 Reduction of thickness of dermal
connective tissue
 Upperback and lumbar sacral area
 Benign course, usually resolve after few
months or few years.
 No effect treatment
 Variant of morphea.
Linear Scleroderma
 Linear lesions extend to length of arms or
leg
 Begin first decade of life
 May also occur parasagitally down the
forehead, known as en coup de sabre
 Parry-Romberg syndrome: progressive
facial hemiatrophy, epilepsy, exophalmos,
and alopecia, maybe a form of linear
scleroderma.
CREST Syndrome
 AKA Thibierge-Weissenbach Syndrome.
 Systemic sclerosis may be limited to the
hands, and is called acroslerosis.
 Not as severe as PSS
 ANA shows anticentromere antibody, and is
highly specific.
 Most favorable diagnosis
Progressive Systemic Sclerosis
 Raynaud’s is the first manifestation of PSS
most of the time and is eventually nearly
always present
 Round fingerpad sign: loose the normal
peaked contour and appear round from the
side.
 Pterygium inversum unguis: distal part of
nailbed remains adherent to ventral surface
of nail plate. Seen also in LE
Progressive Systemic Sclerosis
 75% have dilated nail fold capillary loops
 Esophageal involvement in 90% of patients
 Pulmonary fibrosis
 Cardiac involvement
 Articular pain, swelling, polyarthritis.
Prognosis
 Skin involvement after 1 year of diagnosis:
 Group I – sclerodactyly alone – 71% 10
year survival rate
 Group II - Skin stiffness above metacarpalphalangeal joints but not involving trunk –
58% survival rate.
 Group III – truncal involvement – 21%
survival.
LAB Finding
 Topoisomerase I (formerly Scl–70) is
present in 20-30% of patients with diffuse
disease (absent in limited disease) and has
an increased association with pulmonary
fibrosis
 Anticentromere antibodies are present in
about 60-90% of patients with limited
disease and 10-15% with diffuse disease.
Histology
 Increased collagen bundle and thickness of
the dermis
 Pilosebaceous units are absent. Eccrine
glands and ducts are compressed by
collagen.
 Eccrine glands present at the mid dermis
rather than at the junction of dermis/subQ
fat.
Treatment
 Symptomatic tx
 Treatment aimed at minimizing
complications
 Regular massage, warmth, and protection
from trauma
 No smoking
Eosinophilic Fasciitis
 Patient engaging in strenuous muscular effort few
days or week before acute onset of weakness.
Follow by severe induration of the skin and subQ
tissue of forearms and legs.
 Coarse peau d’orange appearance.
 Groove sign: depression follows the course of
underlying vessels when arms are held laterally.
Represents line of demarcation between muscle
groups
 Excellent response to corticosteroid.
Comparison of deep morphea and eosinophilic fasciitis. A Note the
‘pseudo-cellulite’ appearance of the involved skin of the thigh
in deep morphea. B In eosinophilic fasciitis, the level of
fibrosis is also deep.
Histology
 Patchy lymphocytic and plasma cell
infilrate in the fascia and subfacial muscle
and great thickening, 10-50 times normal of
the fascia.
Mixed Connective Tissue Disease
 Mixed features of scleroderma, SLE, and
dermatomyositis
 IgG deposition in speckled (particulate)
pattern in epidermal nuclei of normal skin
on DIF is a distinctive finding in MCTD
 Treatment with daily dose of prednisone
1mg/kg shows good improvement.
 Most patients have anti-U1RNP antibodies
Sjogren’s Syndrome
 AKA Sicca syndrome
 Triad of keratoconjunctivitis sicca, xerostomia,
and rheumatoid arthritis.
 RF is usually positive
 Elevated C-reactive Protein, IgG, IgA, and IgM
 80% has anti-Ro/SSA antibody.
 >50% have anti-La/SSB antobodies
 Only symptomatic treatment available.
 Labial salivary gland biopsy most definitive test
Schirmer test
 Assesses lacrimal
gland function
 Whatman paper wick
folded over eyelid for
5 minutes
 <5mm tear film
migration = lacrimal
gland dysfunction
Rheumatoid Nodules
 20-30% of RA patients
 Subcutaneous nodules
 Found anywhere on the body
 Histologically shows dense foci of fibrinoid
necrosis surrounded by histiocytes in
palisaded arrangement.
Relapsing Polychondritis
 Intermittent episodes of inflammation of the
articular and nonarticular cartilage
eventuating in chondrolysis.
 MAGIC syndrome = Behcet’s + Relapsing
Polychondritis (Mouth And Genital ulcers
with Inflamed Cartilage)
 Treatment with Dapsone for few weeks,
then maintenance for 4-6 asymptomatic
months.