Download A CASE OF SEPTIC SHOCK - ERYTHEMA NODOSUM LEPROSUM

A CASE OF SEPTIC SHOCK ERYTHEMA NODOSUM LEPROSUM
Vinodkumar Radhakrishnan(1), G.Vasumathi(1), A.Ramalingam(1),S.M.Sujatha(1)
Abstract
Hansens Disease is one of the common treatable dermato-neurologic manifestations of a chronic granulomatous infectious disease. ENL or Type 2 Lepra reaction is an immune complex hypersensitivity phenomenon occurring in patients with
polar or borderline lepromatous leprosy. It affects skin, peripheral nerves & mucous membranes. It follows initiation or
completion of leprosy treatment in 90% of cases but can rarely precede treatment. This case describes a Lepra Reaction
presenting with septic shock as a first manifestation even before treatment initiation. Patients may present with ENL as
their first manifestation of leprosy which predominantly presents as crops of painful erythematous nodules and in severe
cases it presents with fever, uveitis, arthritis, hypotension and tachycardia which mimics septic shock and can be lifethreatening. This case illustrates the importance of diagnosing an immune reaction in the setting of leprosy and clinical
suspicion and recognition of this syndrome is critical to instituting appropriate therapy at early stage to prevent damaging
effects.
KEY WORDS
Hansens disease, Lepra Reaction, Erythema Nodosum Leprosum (ENL), Septic Shock.
INTRODUCTION:
Lepra Reactions are immunological phenomenon caused by
acid fast bacilli affecting skin peripheral nerves and mucous
membranes. It can occur before during or after completion
of MDT for Leprosy. This case describes a lepra Reaction
presenting with systemic manifestation before treatment
initiation in the form of septic shock as a first manifestation. Patients may present present with ENL initially seen
as crops of painful erythematous nodules and in severe
cases it presents with fever, uveitis, arthritis, hypotension
and tachycardia which mimics septic shock and can be lifethreatening. This case illustrates the importance of diagnosing an immune reaction in the setting of leprosy and clinical suspicion and recognition of this syndrome is critical
to instituting appropriate therapy at early stage to prevent
damaging effects.
CASE REPORT :
We had a 24 yrs female admitted in our emergency departement with high grade fever and myalgia for 2 weeks and she
was dyspnoeic in a critically ill state. She also had history
of headache and vomiting. Her past medical history was
insignificant except for history suggestive of allergic skin
rashes. She was drowsy but oriented, febrile, dehydrated. BP
– 80/60 mm/hg PR – 120/min regular RR – 24 /min .Her
systemic examination was unremarkable including eyes and
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joints. She had multiple small irregular erythematous maculo-papular & nodular eruptions and infiltrated plaques.
They were non itchy and tender seen on her face, trunk, abdomen, back and limbs. Multiple chronic atrophic patches
were seen over both leg and forearm. Genitals, palm and
sole were normal. She had diffuse hair loss but peripheral
nerves had no thickening.
Inv: CBC: HB 11.6 gm% Total counts – 21,000 cells/cu.mm
P 80 L15 E2 M3% PLT 2.9 lakhs. RFT: WNL, LFT: T.B – 0.8,
T.P-6.9, Alb-4.3 g/dl, SGOT-62, SGPT-92, ALP-127
CXR: NAD; ECG: Sinus Tachycardia
CRP: Positive 13 mg/L ESR: 43 mm at first hour - both
raised.
Problems: Fever / maculopaular skin lesions? Acute on
chronic / Sespis / Septic shock.
She was treated with iv crystalloids, Inotropes, antibiotics,
PPI, anti-pyretics, antihistamines and skin emollients. During further stay her fever spiked intermittently.
Skin lesions worsened (figure 1 and 2) and she started to
have severe knee joint pain s/o Arthritis. It was managed
with NSAIDS. In view of persistent fever Antibiotic escalated. Pt still had spikes of Fever, BP Improved.
She started to have an acute onset of visual blurring in right
eye assoc with watering and discomfort. Right eye: - AC
flares cells+ broken synechia - ant capsule involved Visual
1. Department of General Medicine, Stanley Medical College
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Stanley Medical Journal
Figure 1 : Multiple erythematous maculo-papular eruptions and infiltrated plaques
Figure 2: Painful erythematous nodules is a predominant
feature of ENL SKIN LESIONS
acuity 3/60 – 6/36. Impression: Acute Iridocyclitis (figure 3). Hence started on Ciprofloxacin and cyclosporin eye
drops.
We have a patient who presented to us with FEVER
– unresolved with antibiotics - SKIN LESION WORSENING + ARTHRITIS + UVEITIS.
All septic workup turned out to be negative. What is left?
Hansen’s had to be ruled out. Hence we proceeded with a
SSS smear which turned out be POSITIVE for acid fast bacilli and bacillary index varied 3+ to 4+ at different sites.
(Figure 4)
.
OTHER Investigations done:
Finally the skin biopsy done showed epidermal thinning
and atrophy. Rete-ridges were lost while in dermis the subepidermal free zone of Unna (grenz zone) was spared; plenty of neutrophils in the dermis with Virchow Cells (macrophages) VACUOLATED FOAMY CYTOPLASM (figure 5)
seen - feature classical of LEPROMATOUS LEPROSY.
ECHO: Normal No vegetations.
ASO/ ANA/ RF : Negative CPK : 46 IU/L — FLP & Thyroid profile – normal limits;
DIFFERENTIAL DIAGNOSIS: (TABLE 1)
BIOPSY REPORT:
Considering the clinical manifestations in our patient
Table 1: Maculo papular Skin Rash in patients with fever and uveitis.
CTD /vasculitis:
Viral infections: cannot be ruled out
ANA/RF : negative. Pulse - normal
Cutaneous Drug Reactions:
old skin lesions worsening.
Peripheral Smear: inc Neutrophils.
HIV: negative
Syphilis – palms & soles spared VDRL negative, HBsAg
Anti HCV Negative
EM/TEN/SJS/TSS
Tuberculosis/verrucosa cutis :
Mucosal sites are normal. No blisters.
Mantoux - negative, Sputum AFB & C/S : negative
Gram negative sepsis:
Sero Negative Arthritis:
All cultures sterile, Lepto/ WIDAL/ QBC/ MPMF/Dengue
Xray knee /pelvis with Both Hip and LS spine : Normal
: Negative
no other associated symptoms
Uveitis with Skin lesions
Sarcoid /TB: Serum calcium -normal,
Xray Chest : NAD , No hilar Adenopathy
16
Diabetes : RBS normal
Behcets : No oral /genital ulcers
IBD :No symptoms of Altered bowel habits , Stool for ova
cyst : Negative , USG abdomen : NAD
deformity. Two types of reactions1 are recognised: Reversal
Reaction (RR)-TYPE 1 and Erythema Nodosum Leprosum
(ENL) – TYPE 2. Together they may affect 30–50% of all
MB leprosy patients2.
Figure 3 : Iridocyclitis
FINAL DIAGNOSIS:
Hence with her dramatic inflammatory presentation final
diagnosis was established as LEPROMATOUS LEPROSY
IN TYPE 2 LEPRA REACTION – Erythema nodosum leprosum (ARTHRITIS +UVEITIS + SEVERE SKIN ERUPTIONS) possibly VIRAL EXANTHEMA precipitating ENL.
TREATMENT:
Hence she was started on MB-MDT regimen and Steroids
and she showed dramatic clinical improvement and discharged. Her follow up over the next four months was also
uneventful.
DISCUSSION:
Hansens Disease is one of the common treatable dermato-neurologic manifestations of a chronic granulomatous infectious disease. Because M. leprae infects peripheral nerves, the inflammation associated with reactions
is a medical emergency. Severe nerve injury may develop
rapidly, with subsequent loss of sensation, paralysis and
Figure 4 : SLIT SKIN SMEAR
Multiple pink coloured Acid fast solid staining rods in
groups on a background of neutrophils
Reversal Reaction: Occurrence of either or both of the following in a patient with leprosy (mostly borderline forms)
namely increased inflammation of skin lesions, inflammation of nerves (manifesting as new motor/ sensory impairment, nerve pain or tenderness) may show increased function loss, and sometimes acral edema. T1R could occur
before, during or after treatment with multi drug therapy
(MDT). The majority (about 50%) of reactions occur during treatment with MDT but approximately 25% of patients
present with a type 1 reaction at the time of diagnosis. Approximately 30% of patients with borderline leprosy go on
to develop T1R at some point during their illness3.
ENL or type II reaction is an immunological phenomenon
with the involvement of both the humoral and cell mediated
immune responses to Mycobacterium Leprae with elevated
levels of TNF alpha4. ENL may occur following initiation of
leprosy treatment in 90% of cases but can rarely precede4
or even follow completion of treatment as in our patient.
It can occur as a single acute episode, but frequently develops into a chronic condition with recurrent episodes5. Immune responses causing ENL are triggered by high loads of
fragmented bacilli in skin tissue6. ENL usually occurs in
leprosy patients classified as lepromatous (LL) or borderline
lepromatous leprosy BL (Ridley-Jopling), comprising the
multi-bacillary (MB) patient group, as defined by WHO.
There is occurrence of crops of tender erythematous subcutaneous nodules often in the face or extensor surfaces of
Figure 5 : SKIN BIOPSY
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the limbs as a predominant feature. There may be associated
systemic illness like fever, malaise, weight loss, peripheral
oedema, arthralgia / arthritis, bone pain7. Severe ENL reaction is often recurrent and chronic and may vary in its
presentation like multiple ulcerating pustular nodules, or
neuritis. Recurrence is the rule rather than the exception.
Involvement of other organs (e.g. eyes, testes, lymph nodes
and joints) sometimes arthritis occurs, or lymphadenitis,
orchitis may be encountered as well as iridocyclitis and
glaucoma which can lead to blindness. Hypotension and
tachycardia can occur which may mimic septic shock and it
can be life-threatening7, 8.
General principles of Management: Systemic corticosteroids are the first line of treatment for 12 weeks accompanied
with MDT regimen9. Management with corticosteroids: If
still on anti-leprosy treatment, continue the standard course
with MDT. Use adequate doses of analgesics to control fever and pain. Use standard course of prednisolone in dosage
per day not exceeding 1 mg/Kg body weight. Management
with clofazimine and corticosteroids is indicated in cases
with severe ENL who are not responding satisfactorily to
treatment with corticosteroids or where the risk of toxicity
with corticosteroids is high. Start clofazimine 100 mg three
times a day for maximum of 12 weeks. Complete the standard course of prednisolone. Taper the dose of clofazimine
to 100 mg twice a day for 12 weeks and then 100 mg once a
day for 12-24 weeks. If the MDT treatment is already completed there is no need to restart MDT. It takes about 4-6
weeks for clofazimine to take full effect in controlling ENL.
Other drug claimed to be useful in ENL is pentoxifylline10,
11 alone or in combination with clofazimine/prednisolone. Due to the well-known teratogenic side effects World
Health Organisation does not support the use of thalidomide in the management of ENL. Cyclosporine has been
used with mixed results12. Azathioprine and methotrexate
have been used in combination with prednisolone for treatment of Type 2 reactions and may offer a steroid sparing
regimen for treatment 13.
In our patient Lepra reaction (ENL) presented as a first
manifestation of Leprosy associated with septic shock14.
Further she had no classical features of leprosy like hypoanesthetic patches, peripheral nerve thickening, sensory
symptoms or trophic ulcers which makes this case unique.
This case mainly illustrates the importance of diagnosing
an immune reaction in the setting of leprosy. Unusual presentation of leprosy should be clinically suspected and recognized as it is critical for instituting appropriate therapy
at early stage to prevent damaging effects. Hence increased
awareness may avoid delay in diagnosis.
REFERENCES:
1.
WHO Expert Committee on Leprosy (2010: Geneva, Switzerland).Global leprosy situation, 2010. Weekly
epidemiological record 85: 337–348.
2.
Scollard DM et al. The continuing challenge of leprosy. Clinical Microbiology Reviews, 2006, 19:338–381.
3.
Leinhardt C, Fine PEM. Type 1 reaction, neuritis
and disability in leprosy: What is the current epidemiological situation? Leprosy Review 1994; 65: 9 - 33
4.
Pocaterra L, Jain S, Reddy R et al. Clinical course
of erythema nodosum leprosum: an 11-year cohort study in
Hyderabad, India. Am J Trop Med Hyg 2006; 74: 868-7
5.
Myerson M. Erythema Nodosum Leprosum. International Journal of Dermatology, Vol. 35, June 1996.
6.
Wemambu SNC, Turk JL, Waters MFR, Rees RJW
(1969) Erythema nodosum leprosum: a clinical manifestation of the arthus phenomenon. The Lancet 294: 933–935.
7.
A Systematic Review on the Epidemiological Data
of Erythema Nodosum Leprosum, a Type 2 Leprosy Reaction. Carlijn G. N. Voorend, Erik B. Post*The Royal Tropical
Institute (KIT Health), Amsterdam, The Netherlands
8.
Van Veen NH, Lockwood DN, Van Brakel WH,
Ramirez Jr J, Richardus JH (2009) Interventions for erythema nodosum leprosum. A Cochrane review. Lepr Rev 80:
355–372
9.
Welsh O et al. A new therapeutic approach to type
II leprosy reaction. International J. Dermatology, 1999,38:
931-933.
10.
Nery JA et al. The use of pentoxifylline in the treatment of type 2 reactional episodes in leprosy. Indian J. Leprosy, 2000, 72 (4): 457-467.
11.
Moreira AL et al Comparison of pentoxifylline,
thalidomide and prednisone in the treatment of ENL. International Journal of Leprosy and Other Mycobacterial Diseases, 1998, 66:61–65.
12.
Mascarell L, Truffa-Bachi P. New aspects of cyclosporin A mode of action: from gene silencing to gene upregulation. Mini Reviews in Medicinal Chemistry, 2003,
3:205–214.
13.
Mahajan VK, Sharma NL, Sharma A. Pulse dexamethasone, oral steroids and azathioprine in the management of erythema nodosum leprosum. Leprosy Review,
2003, 74:171–174.
14.
Type 2 Lepra Reaction as a Cause of Pyrexia of Unknown Origin KV Vinod Et al JAPI •April 2012 • Vol 1. 60
ACKNOWLEDGEMENT:
We are thankful to The Department of Dermatology, Stanley Medical College Hospital Chennai – 600 001 for helping
us in Skin Biopsy.