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 Table of Contents  
CASE BASED REVIEW
Year : 2021  |  Volume : 16  |  Issue : 3  |  Page : 345-348

A tale of two great mimickers: leprosy or sarcoidosis? A case-based review


1 Departments of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India
2 Departments of General Pathology, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission18-Dec-2020
Date of Acceptance06-Feb-2021
Date of Web Publication21-Sep-2021

Correspondence Address:
Dr. John Mathew
Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injr.injr_346_20

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  Abstract 


Leprosy and sarcoidosis are chronic multisystem disorders, with clinical features overlapping with each other. The diagnosis requires a thorough clinical, laboratory, histopathological, and radiological examination. Although it is possible to conclude on one particular diagnosis most of the time, in some cases, even after extensive evaluation, it is difficult to differentiate between the two diseases. In such scenarios, treating both the conditions is warranted. Here, we present a case with a diagnostic dilemma between Hansen's disease and sarcoidosis and systematically discuss the specific pointers which can help to differentiate between the two diseases.

Keywords: Granuloma, Hansen's, sarcoidosis, uveitis


How to cite this article:
Padiyar S, Kharkele R, Telugu RB, Rima S, Mathew J. A tale of two great mimickers: leprosy or sarcoidosis? A case-based review. Indian J Rheumatol 2021;16:345-8

How to cite this URL:
Padiyar S, Kharkele R, Telugu RB, Rima S, Mathew J. A tale of two great mimickers: leprosy or sarcoidosis? A case-based review. Indian J Rheumatol [serial online] 2021 [cited 2021 Nov 27];16:345-8. Available from: https://www.indianjrheumatol.com/text.asp?2021/16/3/345/322432




  Introduction Top


Leprosy is a chronic granulomatous infection predominantly affecting the skin and peripheral nervous system, resulting from infection with Mycobacterium leprae.[1] On the other hand, sarcoidosis is an autoimmune disorder of unknown etiology with multisystem involvement.[2] Although both have a different etiology altogether, sometimes, it is difficult to differentiate between the two as they can have similar presentations and histopathological features. Here, we describe a case, wherein differentiation between the two diseases was challenging and highlight specific points that could help us to distinguish between these two diseases.


  Case Report Top


A 50-year-old housewife presented with high-grade intermittent fever for 1 and a ½ years. She also had recurrent episodes of painful erythematous, nonulcerating nodular lesions over the leg which were steroid responsive. She also had bilateral ankle arthritis. She had a history of three episodes of alternating unilateral facial nerve palsy over 1 year, all completely resolved with a short course of steroids. She had tinnitus in both ears without hearing loss. There were floaters in both eyes for 8 months with gradual decrease in the vision. She also had sensory loss and paresthesia over the dorsal aspect of both feet without any motor symptoms. She had a significant weight loss of 16 kg over the past 6 months. On examination, she had well-defined erythematous, tender nodular coin-shaped lesions over the legs without ulcerations. On neurological examination, she had decreased touch and pain sensations over the dorsum of both feet with a weak toe grip. She did not have any thickened nerves or hypopigmented hypoesthetic patches anywhere. Her ophthalmological examination revealed bilateral granulomatous panuveitis. Audiological evaluation revealed mild sensorineural hearing loss. Her systemic examination was unremarkable. At the end of clinical evaluation, the differentials considered were sarcoidosis, medium-vessel vasculitis like antineutrophilic cytoplasmic antibody-associated vasculitis, and infectious causes like tuberculosis (TB) or leprosy.

On laboratory evaluation, she was found to have hemoglobin: 13 (normal: 11–15 g/dl), total leukocyte count: 5700 (normal: 4000–12,000/mm3), platelets: 287,000 (normal: 150,000–450,000/mm3), serum glutamic oxaloacetic transaminase: 26 (normal: 8–40 U/l) and serum glutamic pyruvic transaminase: 22 (normal: 5–35 U/l), total protein: 7.9 (normal: 6–8.5 g/dl), albumin: 5 (normal: 3.5–5 g/dl), total bilirubin: 0.9 (normal : 0.5–1 mg/dl), alkaline phosphatase: 59 (normal 40–125 U/l), and creatinine: 0.57 (normal: 0.5–1.4). LDH: 515 (normal 225–460 U/L), calcium: 9.4 (normal: 8.3–10.4 mg/dl). Antinuclear antibody by indirect immunofluorescence was negative. Antineutrophil cytoplasmic antibodies by enzyme-linked immunosorbent assay was negative. Further evaluation revealed an angiotensin-converting enzyme (ACE) level of 101 IU/L (normal: 8–52 U/l). A Mantoux test was done which was negative. At this point, the differentials were narrowed down to sarcoidosis or infectious causes like TB or Hansen's disease. A nerve conduction study was done which showed sensory axonal polyneuropathy of bilateral lower limbs. A positron-emission tomography showed enlargement and increased uptake in the hilar lymph nodes [Figure 1]. The imaging of the abdomen revealed cecal wall thickening. A colonoscopic biopsy of the cecal wall ruled out the possibility of TB by a negative GeneXpert TB polymerase chain reaction (PCR). Sural nerve biopsy was done which showed epineural and perineural fibrosis with occasional epithelioid histiocytes cuffed by infiltrates of lymphocytes in the epineurium, perineurium, and endoneurium [Figure 2]a and [Figure 2]b. However, modified Ziehl–Neelsen staining done for lepra bacilli was negative. Skin biopsy of the erythematous lesions was taken which was suggestive of borderline tuberculoid Hansen disease type 1 reaction in view of granulomas, nerves entrapped within granulomas, and subepidermal Grenz zone [Figure 3]a and [Figure 3]b. However, in view of preserved reticulin network in the granulomas, sarcoidosis could not be excluded. Acid-fast bacilli (AFB) test and GeneXpert for Mycobacterium tuberculosis were negative on biopsy. Split skin smears for M. leprae were negative.
Figure 1: Positron-emission tomography–computed tomography showing bilaterally enlarged hilar lymph nodes with increased uptake

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Figure 2: (a and b) Nerve with aggregates of epithelioid histiocytes forming ill-defined epithelioid granuloma (a, H and E, ×40; b, H and E, ×100)

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Figure 3: (a and b) Skin with multiple dermal granulomas composed of epithelioid histiocytes and occasional multinucleated giant cells (a, H and E, ×40; b, H and E, ×100)

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In this scenario, since there were more pointers to the possibility of sarcoidosis because of multisystem involvement, bilateral facial palsy, hilar lymphadenopathy, and elevated ACE levels with a failure to identify lepra bacilli in any of the biopsy samples, it was decided to start the patient on steroids and mycophenolate mofetil as a second-line agent. However since we still did have a suspicion of HD, a PCR for M. leprae was sent in the skin biopsy sample, and the patient was discharged.

On follow-up after 6 weeks, the patient reported more remarkable improvement in systemic symptoms with cutaneous symptoms resolving by 50%. The PCR for M. Leprae was followed up, which was positive. At this juncture, since it was impossible to differentiate between the two diseases, she was also initiated on WHO multidrug therapy (MDT) leprosy for 1 year.

She was followed up closely and reported improvement in her visual and neuropathic symptoms and gained weight. Steroids were tapered slowly and she also completed MDT without any major adverse events. On follow-up at 1 year, she had a flare of uveitis which required a short course of oral steroids. During the last follow-up 2 years later, she was asymptomatic, without any new skin lesions, off steroids, and maintained only on hydroxychloroquine and mycophenolate mofetil.


  Discussion Top


Sarcoidosis is a disease with heterogeneous clinical presentations, and the diagnosis is equally challenging as there is a lack of gold standard tests. Our patient had a constellation of clinical findings in the form of panuveitis, cutaneous lesions, hilar lymphadenopathy, neuropathy, and elevated ACE levels. The two close differentials were sarcoidosis and infections like leprosy.

Uveitis occurs in 20%–30% of cases with sarcoidosis.[3] The majority of sarcoid uveitis is bilateral, and in 90% of cases, it is chronic.[4] Dana et al. reported that among 112 patients with uveitis, 28% were anterior, 38% were intermediate, 12% were posterior, and 22% were panuveitis.[4] Another study from Turkey reported that 38% of patients have panuveitis.[5] On the other hand, even though uveitis is seen in leprosy, it is predominantly anterior with a prevalence of 7%–24%[6],[7] Posterior segment involvement is very rare. Anterior uveitis in leprosy is usually a manifestation of antigen–antibody reaction, seen in Type 2 lepra reaction and is rarely seen in tuberculoid spectrum. There were no other ocular signs suggestive of Hansen's disease like supraciliary madarosis and ectropion. Our patient had panuveitis with intermittent exacerbations responding to steroids. Second, the possible clinical picture of Hansen's in our patient was more in the tuberculoid spectrum which is again favoring an argument of uveitis not due to Hansen's disease.

There was recurrent facial nerve palsy and tinnitus in our patient. As per the existing literature, the prevalence of neurosarcoidosis is around 5%–15%, with cranial neuropathies being most common.[8] However, facial nerve involvement is not rare in leprosy. A study published by Kumar S reported a prevalence of 10%–17% for cranial neuropathy, facial, and trigeminal being most common.[9] They can be associated with lagophthalmos and corneal xerosis due to impaired corneal sensations. Superficial nerve enlargement (supra-orbital and greater auricular nerve enlargement) aids in the diagnosis of leprosy. However, our patient had preserved corneal sensations and no thickened nerves.

Arthritis in sarcoid can be of two types: the more common acute type (25%), which is associated with Lofgren syndrome, or the less common chronic type (1%–4%) which has rheumatoid arthritis (RA) like presentation.[10] However, arthritis in leprosy can manifest in the form of Charcot's arthropathy, acute symmetrical polyarthritis, or swollen hand and feet syndrome as a part of lepra reactions and insidious-onset chronic symmetrical polyarthritis mimicking RA or tenosynovitis.[11] Other than arthritis of lepra reactions, all of them respond only to MDT for leprosy. Arthritis responded to steroids in our patient.

The sensitivity and specificity of serum ACE of more than 100 IU/L for the diagnosis of sarcoidosis are 37% and 94%, respectively.[12] However, ACE levels can be elevated in leprosy, but an elevation greater than two times the upper limits of normal is much less common.[13] However, in one study, the ACE levels in leprosy were low due to an immunodeficiency state.[14] Our patient had ACE values of more than 100 IU/L favoring sarcoidosis.

In our patient, nerve biopsy showed epineural and perineural fibrosis with occasional epithelioid histiocytes which are cuffed by infiltrates of lymphocytes. Cuffed granulomas are more suggestive of an infectious cause because in sarcoidosis, typically, uncuffed or naked granulomas are seen.[15] However, modified Ziehl–Neelsen staining done for lepra bacilli was negative. Skin biopsy of the erythematous lesions was taken which was suggestive of borderline tuberculoid HD type 1 reaction. However, the reticulin network in the granulomas was preserved, which is usually destroyed and fragmented in tuberculoid leprosy.[16] To differentiate the two, a PCR for M. leprae was sent from the cutaneous lesions which were positive.

PCR for detection of M. leprae-specific genes or repeat sequences is highly sensitive and specific, as it detects M. leprae DNA in 95% of multibacillary and 55% of paucibacillary patients.[17] In a Brazilian study, the specificity of this PCR was 100%.[18] After an extensive review of the literature, we found three case reports of concomitant leprosy and sarcoidosis[19],[20],[21] [Table 1]. All three cases had hilar lymphadenopathy with an inadequate response to MDT, which is unusual in HD. [Table 2] summarizes the differentiating features between an HD and sarcoidosis. Since there was enough evidence for sarcoidosis and with the M. leprae PCR being positive, it was decided to treat the patient for both sarcoidosis and leprosy with which the patient improved. MDT was stopped after 1 year and there have been no relapses in her cutaneous lesions. Our case was a challenge for diagnosis and management and was an example of an overlap of autoimmune disease and infection. The complex immunology at play here is still not understood.
Table 1: Summary of cases published in literature of concomitant leprosy and sarcoidosis

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Table 2: Differentiating features of leprosy and sarcoidosis

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  Conclusion Top


Leprosy and sarcoidosis can mimic each other and also co-exist rarely. Clinicians need to be aware of the presentations and various pointers to differentiate between the two diseases.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed


  Acknowledgments Top


We would like to thank the Departments of Microbiology, Radiology, and Nuclear Medicine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Chavarro-Portillo B, Soto CY, Guerrero MI. Mycobacterium leprae's evolution and environmental adaptation. Acta Trop 2019;197:105041.  Back to cited text no. 1
    
2.
Llanos O, Hamzeh N. Sarcoidosis. Med Clin North Am 2019;103:527-34.  Back to cited text no. 2
    
3.
Coutinho I, Furtado AB, Santos C, Pina S, Lisboa M, Ferreira I, et al. Ocular sarcoidosis: Our reality for the past six years. Rev Bras Oftalmol 2016;75:103-8.  Back to cited text no. 3
    
4.
Dana MR, Merayo-Lloves J, Schaumberg DA, Foster CS. Prognosticators for visual outcome in sarcoid uveitis. Ophthalmology 1996;103:1846-53.  Back to cited text no. 4
    
5.
Sungur G, Hazirolan D, Bilgin G. Pattern of ocular findings in patients with biopsy-proven sarcoidosis in Turkey. Ocul Immunol Inflamm 2013;21:455-61.  Back to cited text no. 5
    
6.
Rawal RC, Kar PK, Desai RN, Shah BH. A clinical study of eye complications in leprosy. Indian J Lepr 1984;56:232-40.  Back to cited text no. 6
    
7.
Khan T, Awan AA, Kazmi HS, Shah AA, Muhammad S, Muhammad S. Frequency of ocular complications of leprosy in institutionalized patients in NWFP Pakistan. J Ayub Med Coll Abbottabad 2002;14:29-33.  Back to cited text no. 7
    
8.
Lacomis D. Neurosarcoidosis. Curr Neuropharmacol 2011;9:429-36.  Back to cited text no. 8
    
9.
Kumar S, Alexander M, Gnanamuthu C. Cranial nerve involvement in patients with leprous neuropathy. Neurol India 2006;54:283-5.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Chu A, Ginat D, Terzakis J, Seneviratne A, Schneider KS. Chronic sarcoid arthritis presenting as an intra-articular knee mass. J Clin Rheumatol 2009;15:190-2.  Back to cited text no. 10
    
11.
Chauhan S, Wakhlu A, Agarwal V. Arthritis in leprosy. Rheumatology (Oxford) 2010;49:2237-42.  Back to cited text no. 11
    
12.
Khan AH, Ghani F, Khan A, Khan MA, Khurshid M. Role of serum angiotensin converting enzyme in sarcoidosis. J Pak Med Assoc 1998;48:131-3.  Back to cited text no. 12
    
13.
Dhople AM, Howell PC, Williams SL, Zeigler JA, Storrs EE. Serum angiotensin-converting enzyme in leprosy. Indian J Lepr 1985;57:282-7.  Back to cited text no. 13
    
14.
Vinnik LA, Gerovich LM, Balybin ES. Angiotensin converting enzyme in the blood serum of patients with tuberculosis and leprosy. Probl Tuberk. 1990:54-6.  Back to cited text no. 14
    
15.
Ball NJ, Kho GT, Martinka M. The histologic spectrum of cutaneous sarcoidosis: A study of twenty-eight cases. J Cutan Pathol 2004;31:160-8.  Back to cited text no. 15
    
16.
Nirmala V, Chacko CJ, Job CK. Tuberculoid leprosy and tuberculosis skin: A comparative histopathological study. Lepr India 1977;49:65-9.  Back to cited text no. 16
    
17.
Williams DL, Gillis TP, Booth RJ, Looker D, Watson JD. The use of a specific DNA probe and polymerase chain reaction for the detection of Mycobacterium leprae. J Infect Dis 1990;162:193-200.  Back to cited text no. 17
    
18.
Maltempe FG, Baldin VP, Lopes MA, Siqueira VL, Scodro RB, Cardoso RF, et al. Critical analysis: Use of polymerase chain reaction to diagnose leprosy. Braz J Pharm Sci 2016;52:163-9.  Back to cited text no. 18
    
19.
Burdick AE, Hendi A, Elgart GW, Barquin L, Scollard DM. Hansen's disease in a patient with a history of sarcoidosis. Int J Lepr Other Mycobact Dis 2000;68:307-11.  Back to cited text no. 19
    
20.
Malkani R, Karia R. Leprosy or sarcoidosis? A diagnostic dilemma! J Family Med Prim Care 2018;7:1106-8.  Back to cited text no. 20
    
21.
Sharma P, Kar HK, Singh B, Deepak D, Bhardwaj M. Systemic sarcoidosis in a case of lepromatous leprosy: A case report. Indian J Lepr 2008;80:275-8.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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