Type II reaction without erythema nodosum leprosum masquerading as lymphoma
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1 Lepr Rev (2012) 83, CASE REPORT Type II reaction without erythema nodosum leprosum masquerading as lymphoma RAHUL MAHAJAN*, SUNIL DOGRA*, INDERJEET KAUR*, SAVITA YADAV*, UMA NAHAR SAIKIA** & ANIL BUDANIA* *Department of Dermatology, Venereology, and Leprology, Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh , India **Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh , India Accepted for publication 28 September 2012 Summary Lepromatous leprosy is a multisystem disease that can involve many organ systems, with lymph nodes a common extra-cutaneous site to be affected. Rarely, multibacillary leprosy can be confused with other diseases like lymphomas and connective tissue diseases. Herein we report a patient of lepromatous leprosy with Type II lepra reaction involving lymph nodes who presented with generalised lymphadenopathy, acquired ichthyosis and constitutional symptoms but no cutaneous lesions to suggest erythema nodosum leprosum, and who was initially misdiagnosed as a case of Hodgkin s lymphoma Introduction Mycobacterium leprae, the causative organism of leprosy primarily affects Schwann cells, endothelial cells and monocyte-macrophage system. 1 Approximately one-third of patients may present with Type II lepra reaction (erythema nodosum leprosum) at the time of diagnosis. 2 Generalised lymphadenopathy as a presenting manifestation of lepromatous leprosy (LL) has been rarely described. 3 5 We report a patient having generalised painful/ tender lymphadenopathy and acquired ichthyosis who was initially diagnosed with TB Lymphadenitis, then Hodgkin s lymphoma but later was found to have lepromatous leprosy and Type II Lepra reaction. Correspondence to: Sunil Dogra, Assistant Professor, Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India (Tel: þ ; Fax No: þ ; sundogra@hotmail.com) /12/ $1.00 q Lepra
2 Type II reaction masquerading as lymphoma 379 Report of a case A 36-year-old male was referred with recurrent episodes of high-grade fever of 12 months duration, plus burning sensation and pain in his hands and feet for 10 months. During the febrile episodes, the patient experienced associated pain in the calf muscles, redness of eyes, testicular pain and arthralgia. Almost simultaneously he noticed the development of dry, scaly lesions over both lower limbs and upper limbs. After nearly 8 months he developed painful nodular swellings over the axillae and inguinal regions. Fine needle aspiration cytology (FNAC) from the axillary swelling revealed granulomatous pathology and hence, with a possible diagnosis of tuberculosis, he was started empirically on anti-tubercular therapy with no significant clinical improvement. A lymph node biopsy from axilla was reported elsewhere as Hodgkin s lymphoma. Finally, the patient was referred to the hematology unit of our institute for the management of suspected lymphoma and a dermatology opinion was sought for the management of his skin lesions. A general physical examination revealed fever (398C), pallor, hepato-spleno-megaly along with cervical, axillary and inguinal lymphadenopathy. Lymph nodes were multiple, firm to hard in consistency, tender and mobile. Mucocutaneous examination showed diffuse infiltration of the face including ear lobules and skin coloured papules and nodules over the forehead and ear lobes (Figure 1). Over the upper and lower limbs, areas of ichthyosis were present (Figure 2). Sensory examination revealed glove and stocking anesthesia. Bilateral supra-clavicular, ulnar, median, radial-cutaneous, lateral popliteal and posterior tibial nerves were thickened. Motor examination did not reveal any muscle weakness. INVESTIGATIONS AND COURSE A complete blood count showed anemia with no atypical cells on peripheral smear examination. A slit skin smear showed bacteriological index to be 5 þ on the Ridley scale and morphological index was 0%. A second FNAC from axillary lymph nodes showed Figure 1. Diffuse infiltration seen over the face, especially forehead and ear lobes.
3 380 R. Mahajan et al. Figure 2. Areas of ichthyosis present over both lower limbs. organised inflammation. Histopathology of skin biopsy from lower back showed thinned out flattened epidermis; periadnexal, perivascular and perineural circumscribed epithelioid cell granulomas and Langhan type giant cells with collection of foamy histiocytes in the dermis (Figure 3). Histopathological examination of axillary lymph node revealed extensive effacement of architecture with numerous epithelioid cell granulomas having central polymorphic collection and nuclear debris and scattered multinucleated giant cells (Figure 4). No acid fast bacilli (AFB) could be demonstrated on skin or lymph node biopsy specimens. Based on the clinical and histopathological findings, a diagnosis of untreated Figure 3. H & E (X 100) Skin biopsy showing epithelioid cell granulomas and Langhan giant cells with foamy histiocytes.
4 Type II reaction masquerading as lymphoma 381 Figure 4. H & E (X 100) Lymph node biopsy showing effacement of architecture with epithelioid cell granulomas, central collection of polymorphs and nuclear debris. LL with Type II reaction involving lymph nodes was made. The patient was started on WHO-recommended multidrug therapy, multibacillary regimen (MDT-MB). For Type II lepra reaction, oral prednisolone (starting at 60 mg/day followed by tapering to 40 mg/day), clofazimine 300 mg/day along with antipyretics were prescribed. Within 2 weeks of starting treatment, he showed significant improvement in his general condition and subsidence of enlarged lymph nodes. Discussion Although the clinical diagnosis of leprosy is rarely difficult in the presence of hypopigmented hypo-aesthetic patches, it may pose a diagnostic challenge in certain situations. There are several case reports in literature where leprosy has been confused with other diseases, common mimicrs being sarcoidosis, 6 cutaneous lymphomas, 7,8 Jessner s lymphocytic infiltrate, 9 multicentric reticulohistiocytosis, 10 and connective tissue diseases. 11,12 Balachandran et al. have reported two cases of non-hodgkin s lymphoma and histiocytic lymphoma simulating lepromatous leprosy. 8 In addition, there are many reports of association of leprosy with lymphomas. 13 Leprosy can also mimic or coexist with connective tissue diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis. 11,12 Autoaggressive hanseniasis refers to a syndrome with immunopathologic and clinical features simulating auto-aggressive diseases. The exact aetiopathogenesis of this condition is not
5 382 R. Mahajan et al. known but may be caused by B cell stimulation along with a dysfunction of the T-suppressor lymphocytes. 14 Lymph node involvement in leprosy can be due to Type II reaction or as a part of visceral involvement in lepromatous leprosy. Satti et al. recognised Hansen s disease to be an important cause of lymphadenopathy in endemic areas. 15 Gupta et al. studied the aspiration cytology of lymph nodes in leprosy and found 51 7% to have Type 1 and 25% to have Type II pattern with both patterns showing predominantly foamy histiocytes and corresponding to lepromatous spectrum of disease. A Type III pattern was seen in 16 6% patients, showing atypical histiocytes due to improved cell mediated immunity and corresponding to borderline spectrum, and another 6 7% patients showed a Type IV pattern with predominant epithelioid histiocytic cell population, analogous to tuberculoid spectrum of Hansen s disease. 16 Rodriguez reported a case of Type II reaction presenting with generalised lymphadenopathy. 5 Bagla et al. reported a 70 year old male presenting with generalised lymphadenopathy and a clinical suspicion of Hodgkin s disease. Histopathologic examination of cervical and axillary lymph nodes revealed aggregates of lepra cells loaded with lepra bacilli. 3 Singh et al. reported two cases, one with localised and other with generalised lymphadenopathy who were initially diagnosed as tuberculosis and lymphoma respectively, and later only on lymph node biopsy was a diagnosis of leprosy made. 4 In the present case, the patient presented with constitutional symptoms, generalised lymphadenopathy, splenomegaly and acquired ichthyosis, all of which could be clinically consistent with lymphoma. However, tender lymphadenpopathy is not usually seen in tuberculosis and lymphoma as they are usually painless. Hence, these features should lead the physician to suspect an alternate aetiology. Presence of cutaneous infiltration over face and thickened peripheral nerves along with sensory anesthesia should have raised the suspicion of leprosy, although the typical lesions of erythema nodosum leprosum seen in Type II reaction were missing. Finally, a simple test like slit skin smear should suffice to rule out leprosy aetiology in this clinical situation, along with a search for the other cardinal signs of thickened peripheral nerves or hypo-anaestehetic skin patches and for immunosuppression. The present case serves as an important reminder that the level of suspicion in diagnosing leprosy should remain high when encountering symptoms suggestive of connective tissue diseases or lymphadenopathy especially in regions where leprosy is currently or was earlier endemic. References 1 Ramesh V, Kumar J. Systemic manifestations. In: Kar HK, Kumar B (eds). IAL Textbook of leprosy. 1 st edition, Jaypee Brothers, New Delhi, 2010; pp Kumar B, Dogra S, Kaur I. Epidemiological characteristics of leprosy reactions: 15 year experience from North India. Int J Lepr Other Mycobact Dis, 2004; 72: Bagla N, Patel MM, Patel RD, Jarag M. Lepromatous lymphadenitis masquerading as lymphoma. Lepr Rev, 2005; 76: Singh PK, Agarwal A, Rajvanshi VS, Agarwal U. Lymphadenopathy in leprosy with unusual presentation. Indian J Lepr, 1985; 57: Rodriguez G. Generalized adenopathy as a manifestation of type 2 reactional leprosy. Biomedica, 2003; 23: Singh K, Raina V, Narulla AK, Singh R. Sarcoidosis masquerading as leprosy, pulmonary tuberculosis and urolithiasis. J Asso Phys India, 1990; 38: Balachandran C, Srinivas CR, Senoy SD, Ramnarayan K. Cutaneous lymphoma masquerading as lepromatous leprosy. Int J Lepr & Othr Mycobact Dis, 1990; 58:
6 Type II reaction masquerading as lymphoma Balachandran C, Srinivas CR, Singh KK, Venugopal N. Histiocytic lymphoma simulating lepromatous leprosy. Indian J Lepr, 1987; 59: Singh K, Dawar R, Ramesh V. Lymphocytic infiltration of skin of Jessner-Kanof masquerading as borderline leprosy. Indian J Lepr, 1985; 57: Razack EM, Dharmaraj S, Krishnaram AS, Selvaraj AM. Multicentric reticulohistiocytosis masquerading as lepromatous leprosy. Indian J Lepr, 1988; 60: Kaur MR, Grindulis K, Maheshwari M et al. Delayed diagnosis of leprosy due to presentation with a rheumatoidlike polyarthropathy. Clin Exp Dermatol, 2007; 32: Aliberti JR, Cabrera A, Martiniuk F et al. Leprosy masquerading as lupus. J Am Acad Dermatol, 2005; 52: Sethuraman G, Serisha, Srinivas CR et al. Leprosy with peripheral T cell lymphoma: a rare association. Int J Lepr Other Mycobact Dis, 2001; 69: Azulay RD. Autoagressive hanseniasis. J Am Acad Dermatol, 1987; 17: Satti MB, al-mohaya S, Omer AS. Hansen s disease: a cause of lymphadenopathy in endemic areas. Trop Geogr Med, 1989; 41: Gupta SK, Kumar B, Kaur S. Aspiration cytology of lymph nodes in leprosy. Int J Lepr Other Mycobact Dis, 1981; 49: 9 15.
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