Cutaneous Sarcoidosis Misdiagnosed as Leprosy. Report of Two Cases and Review of Literature
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1 Indian J Lepr 2016, 88 : Hind Kusht Nivaran Sangh, New Delhi Case Report Cutaneous Sarcoidosis Misdiagnosed as Leprosy. Report of Two Cases and Review of Literature KN Chowdhary, R Rao, P Priya, M Valiathan, S Shetty, S Pai Received : Accepted : Cutaneous sarcoidosis may occasionally be mistaken and treated for leprosy. We present two cases of sarcoidosis of the skin which were initially treated as leprosy based on the histopathological features. Histological study in one patient showed perineural and perivascular granuloma adding on to the diagnostic confusion. It is very important for the clinicians to consider sarcoidosis as a possible diagnosis in a patient with clinical features that are not typical of leprosy. Histopathology along with appropriate in -situ techniques can help in arriving at an appropriate diagnosis. Key words : cutaneous sarcoidosis, leprosy, differential diagnosis Introduction Sarcoidosis is an idiopathic, multisystem granulomatous disease, that commonly affects the lungs, eyes, lymph nodes and the skin. Sarcoidosis can mimic many medical diseases including leprosy. Leprosy and sarcoidosis share several common clinical and histopathological features leading to diagnostic confusion (Kaur et al 1993). In leprosy endemic regions of the world, it is likely that sarcoidosis of the skin can occasionally be misdiagnosed as leprosy. We report two cases of cutaneous sarcoidosis diagnosed and treated initially as leprosy due to misdiagnosis. Brief Case Reports Case 1 A 62-year-old male with no co-morbid illnesses presented with asymptomatic, red, annular lesions over the scalp and the upper limb. These were present since the last 10 years. He initially noticed red, ring like lesions on the scalp, which gradually enlarged to cover large part of his scalp. Subsequently, similar lesions appeared on the forehead and right elbow. He consulted a dermatologist at a local hospital where he underwent a skin biopsy. Histopathology showed 1 K Neethu Chowdhary 2 R Rao, MD, Additional Professor, Department of Dermatology 3 P Priya 4 M Valiathan 5 S Shetty 6 S Pai Kasturba Medical College, Manipal, Karnataka, India Corresponding author : Dr Raghavendra Rao. raghavendrarao1@gmail.com
2 178 Chowdhary et al Fig 1 : Erythematous annular plaques (a) over the forehead; (b), elbow; (c & d) over the scalp (Case 1) Fig 2 : Numerous epithelioid cell granulomas in the dermis comprising of epithelioid cells, Langhan's type of giant cell, lymphocytes H&E X100 in (a), (b) same under X200 magnification. (Case 1)
3 Cutaneous Sarcoidosis Misdiagnosed as Leprosy. Report of Two Cases and Review of Literature 179 Fig 3 : (a) Chest X-ray showing prominent hilar lymph nodes. (b) High resolution CT showing enlarged hilar lymph nodes (indicated by arrow) in Case 1. features of tuberculoid granuloma and he was commenced on multi-bacillary, multi drug therapy (MB-MDT) for leprosy, which the patient took for 18 months without much improvement. On the contrary, he started developing new lesions since the last two months, while still on medications; hence he decided to take a second opinion from us. Clinical examination revealed erythematous annular plaques with central clearing and raised borders over right side of forehead, scalp, on both elbows and right knee (Fig 1). There was no nerve thickening and sensation over the lesions was intact. Slit skin smear (SSS) from the standard sites were negative. Repeat skin biopsy showed numerous epithelioid cell granulomas with 'Langhans' type giant cells (Fig 2). Chest x-ray showed prominent hilum and high resolution computerized tomography (HRCT) of the chest showed bilateral hilar lymphadenopathy (Fig 3). Mantoux test was non-reactive (4 mm at 48 hours) and serum angiotensin converting enzyme (ACE) levels was raised - 91 µg/l (normal 8-65 µg/l). A diagnosis of sarcoidosis was considered and the patient was started on oral hydroxychloroquine (400 mg/day) along with weekly methotrexate (7.5mg/week). The patient responded to the treatment.
4 180 Chowdhary et al Fig 4 : Erythematous, infiltrated plaques and nodules on the (a) cheek and ala nasi (b), arm (c) dorsum of hands (d) ear lobule of case 2. Case 2 A 43-year-old man presented with asymptomatic red nodules over the extremities, back and face since last 5 years. He initially consulted a local dermatologist who performed a skin biopsy. Based on the biopsy report, he was treated for leprosy with MB-MDT for one year with which the lesions healed leaving behind atrophic scars. However, since te last one year, he again started noticing erythematous infiltrated lesions over dorsal inter phalengeal (DIP) joints, external nares, ear lobules, back and arms (Fig 4). Sensations over the lesions were intact and there was no peripheral nerve thickening. Slit skin smear (SSS) for acid fast bacilli was negative; histopathology of the biopsy showed perneurovascular and peri-apendageal granulomas with epithelioid cells surrounded by lymphocytes (Fig 5). Serum ACE level was marginally raised (66µg/L; normal being 8-65). Chest x-ray showed bilateral hilar lymphadenopathy (Fig 6); he however, did not consent for HRCT.
5 Cutaneous Sarcoidosis Misdiagnosed as Leprosy. Report of Two Cases and Review of Literature 181 Fig 5 : Perivascular and perineural (marked by arrow), discrete as well as confluent granulomas composed of epithelioid cells and lymphocytes (H&E staining [a] X100,[ b] X200) in biopsy from case 2. Fig 6 : Chest X-ray showing prominent hilar lymphadenopathy in case 2. Discussion Cutaneous sarcoidosis is often considered as the great imitators in dermatology as skin lesions assume a vast array of morphological pattern and can mimic many other diseases. Cutaneous manifestations are seen in 1/3rd of the patients with sarcoidosis and are classified into specific or non-specific lesions based on the presence or absence of non-caseating granulomas on histopathology (Munday et al 2015). Common specific lesions include lupus pernio, infiltrative plaques and subcutaneous nodules; rare specific presentations include alopecia, ulcers, hypopigmented patches and ichthyosis. The most common non-specific lesions observed in sarcoidosis is erythema nodosum, which is typically acute in onset. Apart from lupus pernio, all other types of lesions of sarcoidosis can be mistaken with leprosy (Kaur et al 1993). The presence of satellite lesions, peripheral nerve thickening and loss of sensation are the main distinguishing clinical features of leprosy and which help in differentiating leprosy from sarcoidosis. Slit skin smear is generally negative in borderline tuberculoid (BT) leprosy and histopathology shows epithelioid cell granuloma, making its distinction from sarcoidosis difficult.
6 182 Chowdhary et al Table 1 : Main histological features of sarcoidosis and leprosy Features Sarcoidosis Leprosy General structure Monomorphic granulomas Caseating granulomas Granuloma Discrete, sharply defined 'naked granuloma' Confluent, diffuse Giant cells Large, usually sparse Langhans' and More numerous, Langhans' foreign body cells cells predominate Lymphocytes Sparse cuffing: <25% of periphery More numerous and scattered >25% of periphery Asteroid and Present Absent Shaumann bodies Reticulin Fine and abundant around the tubercles Destroyed Healing process Progressive hyalinization from periphery; Dense collagen mesh Retraction, gradual dissolution Fibrosis, and Calcification Fite stain Negative Positive Perineural and Absent Present peri-appendageal granulomas Table 1 summarizes the key histopathological comparison between sarcoidosis and BT leprosy. Kaur et al (1993) reported a case of cutaneous sarcoidosis which was initially treated with MB-MDT; later on the patient presented with relapse and re-appearance of lesions. They did a biopsy from the affected skin lesion, and observed lymphocytic infiltration in the dermis with features suggestive of both leprosy and cutaneous sarcoidosis. They concluded in their study that the presence of granulomatous infiltration in dermal nerves in leprosy is most consistent differentiating feature between the two conditions. Sarcoidosis may also present with perineural granulomatous response (as in our second case) that closely resembles leprosy. AFB staining, use of molecular techniques and PCR studies are helpful in establishing the correct diagnosis (Munday et al 2015). Immunohistochemistry and in-situ hybridization/ amplification techniques aiming at detection of mycobacterium and or M. leprae specific targets have potential application to differentiate such cases. Involvement of nervous system is seen in less than 5% of patients with sarcoidosis ((Said et al 2002). Peripheral neuropathy leading to sensory disturbances is very rare and is seen in less than 20% of cases with neurological involvement in sarcioosis. This is referred to as SSFN or sarcoidosis sensory fibre neuropathy (Munday et al 2015) Symptoms related to sensory disturbances in sarcoidosis may further add on to the diagnostic confusion between leprosy and cutaneous sarcoidosis. In the present series of case reports, our second patient had no neurological symptoms and signs despite showing perineural granuloma on histopathology. Presence of cutaneous anergy (as evidenced by negative intradermal tests to Mantoux, Candidin & Trichophytin) and lack of sensitisation to DNCB are important tests which can be used to differentiate between the two conditions (Kaur et al 1993). In addition demonstration of granulomas in the muscle specimen is characteristically seen in sarcoidosis and has been suggested to be useful in differentiating leprosy
7 Cutaneous Sarcoidosis Misdiagnosed as Leprosy. Report of Two Cases and Review of Literature 183 from sarcoidosis (Said et al 2002). Serum ACE is elevated in 40-90% of patients with sarcoidosis, especially in those with clinically active disease. However, a normal ACE level does not rule out the diagnosis of sarcoidosis ((Costabel 2001 and Jaffrey et al 1982). Further more, elevated ACE levels may also be seen in other granulomatous diseases such as tuberculosis leading to diagnostic confusion. A significantly high serum ACE level (more than 100 IU/L) goes more in favour of sarcoidosis (Khan et al 1998). It is said that the elevated ACE levels reflect the total body granuloma burden and is helpful in monitoring the effect of treatment (Jaffrey et al 1982). The ACE levels were elevated in one of our patient while it was on the higher side of threshold in the other patient. Several drugs including antileprosy drugs such as rifampicin and clofazimine have been found to be useful in the treatment of cutaneous sarcoidosis (Drake et al 2013, Ridder et al 2000). This might explain the temporary improvement of lesions in our second patient, while he was being treated with MDT. In summary, the reported two cases of cutaneous sarcoidosis were misdiagnosed as leprosy and received MDT. Though rare, sarcoidosis may occasionally have perineural granulomas on histopathology, compounding the diagnostic confusion. Nevertheless, presence of atypical clinical picture such as presence of lesions on the scalp, and ala nasi should raise the suspicion of sarcoidosis and ancillary tests such as HRCT, ACE levels should be done in such patients to differentiate the two. References 1. Costabel U (2001). Sarcoidosis: clinical update. Eur Respir J. Suppl. 1 32: Drake WP, Richter KO, Richmond BW et al. (2013) Oral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis: A Randomized, Single-Masked, Placebo-Controlled Study. JAMA Dermatol. 149: Jeffrey P, Callen, MD, Ruth Hanno, MD. (1982). Serum Angiotensin I-Converting Enzyme Level in Patients With Cutaneous Sarcoidal Granulomas. Arch Dermatol. 118: Kaur S, Dhar S, Bambery P, Kanwar AJ, Khajuria A. (1993). Cutaneous sarcoidosis masquerading as relapsed borderline tuberculoid leprosy? Int J Lepr. 61: Khan AH, Ghani F, Khan A et al. (1998). Role of serum angiotensin converting enzyme in sarcoidosis. J Pak Med Assoc. 48: Munday WR, McNiff J, Watsky K et al. (2015). Perineural granulomas in cutaneous sarcoidosis may be associated with sarcoidosis small-fiber neuropathy. J Cutan Pathol. 42: Ridder GJ, Strohhäcker H et al. (2000). Laryngeal sarcoidosis : treatment with the antileprosy drug clofazimine. Ann Otol Rhinol Laryngol. 109: Said G, Lacroix C, Plante-Bordeneuve V et al. (2002). Nerve granulomas and vasculitis in sarcoid peripheral neuropathy A clinicopathological study of 11 patients. Brain. 125: How to cite this article : Chowdhary KN, Rao R, Priya P et al (2016). Cutaneous Sarcoidosis Misdiagnosed as Leprosy. Report of Two Cases and Review of Literature. Indian J Lepr. 88 :
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