|Year : 2018 | Volume
| Issue : 1 | Page : 14-19
Rheumatological manifestations of hansen's disease
Anupam Wakhlu1, Kamal Kumar Sawlani2, D Himanshu2
1 Department of Rheumatology, KGMU, Lucknow, Uttar Pradesh, India
2 Department of Medicine, KGMU, Lucknow, Uttar Pradesh, India
|Date of Web Publication||26-Feb-2018|
Prof. Anupam Wakhlu
Department of Rheumatology, KGMU, Lucknow - 226 001, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Hansen's disease (leprosy) most commonly presents with cutaneous and nerve involvement. Rheumatological manifestations occur commonly but are often under-recognized. Physicians and rheumatologists alike are often perplexed with the rheumatological manifestations, given that these may precede the diagnosis of leprosy or may suggest another disease, in addition to leprosy. We present our experience with patients of leprosy presenting with rheumatological manifestations.
Methods: This was a retrospective study carried out in the Departments of Rheumatology and Medicine, King George's Medical University, Lucknow, a tertiary care hospital in North India. Those patients who had a confirmed diagnosis of leprosy were subsequently included. Demographic details and clinical presentations were documented.
Results: Twenty-nine cases (19 males, mean age 38 ± 17.2 years) were included in the study. The mean duration of disease was 20.2 ± 18.4 months. Rheumatological manifestations seen included arthritis (n = 17), tenosynovitis (n = 5), swollen hands and feet syndrome (n = 6), painful swollen feet (n = 2), arthralgias (n = 3), and vasculitis (n = 1). The rheumatological diseases mimicked were rheumatoid arthritis (n = 10) and spondyloarthritis (n = 3), sarcoidosis (n = 2), relapsing polychondritis (n = 1), and vasculitis (n = 1). At some point in time, lepra reactions manifesting with arthritis, nodules, tenosynovitis and/or dactylitis were observed in 15 cases. Other classical clinical manifestations detected were paresthesia (n = 13) and anesthetic patches (n = 15). Thickened great auricular, ulnar and lateral popliteal nerve were seen in 20 cases. Five patients had pure neuritic leprosy with no cutaneous manifestations and had arthritis or tenosynovitis.
Conclusion: Leprosy may mimic a number of common and uncommon rheumatological diseases, and these may be the presenting manifestation. Awareness and a high index of suspicion are required to arrive at a timely and accurate diagnosis.
Keywords: Arthritis, Hansen's, leprosy, rheumatological manifestations, tenosynovitis
|How to cite this article:|
Wakhlu A, Sawlani KK, Himanshu D. Rheumatological manifestations of hansen's disease. Indian J Rheumatol 2018;13:14-9
| Introduction|| |
Hansen's disease (Leprosy) is a chronic granulomatous disease caused by Mycobacterium leprae. It most commonly presents with cutaneous and nerve involvement. The prevalence of rheumatic manifestations varies across studies and geographic area, ranging from 1% to 2% in large dermatology series to 60%–80% from rheumatology clinics.,,, Given this reported variability between rheumatologists, physicians and dermatologists, increased awareness for these manifestations are required. Possibly, these manifestations are under-recognized by nonrheumatology services. Atkin et al. reported that approximately 30% of their patients (n = 66) had inflammatory arthritis. Two Indian studies reported prevalence rates for arthritis to be 61.4% and 10%, respectively., Pereira et al. reported a prevalence rate of 6.3% in a cohort of 1257 patients of leprosy. Rheumatic manifestations may be the presenting manifestation of leprosy, and so leprosy may be diagnosed much later, leading to errors or delay in treatment. This study presents our experience of rheumatological manifestations in leprosy mimicking a rheumatic disorder, with leprosy being diagnosed subsequently.
| Methods|| |
This is a retrospective, observational study carried out in a tertiary care Hospital in North India. Patients who had presented with rheumatic manifestations and were confirmed to have leprosy based on clinical examination and investigations were included in the study. Standard WHO criteria were applied to classify a patient as paucibacillary or multibacillary leprosy. Confirmatory investigations included a demonstration of M. leprae by slit skin smear or classical findings on cutaneous or nerve histopathology. Anti-phenolic glycolipid-1 (anti-PGL (1) antibodies were not performed in these patients due to nonavailability. Synovial fluid examination was done where indicated. Specific tests required to investigate the given clinical manifestation as the standard of care were done and included nerve conduction velocity (NCV), sural nerve biopsy, antinuclear antibodies (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and radiological investigations.
Standard WHO recommended treatment protocols for multibacillary and paucibacillary leprosy were followed. Paucibacillary leprosy patients were treated with Rifampicin 600 mg once a month and dapsone 100 mg once a day for 6 months. Multibacillary leprosy patients were treated with Rifampicin 600 mg once a month, Clofazimine 300 mg once a month, dapsone 100 mg once a day, and clofazimine 50 mg once a day for 12 months. The duration of therapy was extended for a further 6–12 months where clinically or bacteriologically indicated. Supportive treatment including nonsteroidal anti-inflammatory drugs (NSAIDs) was used in appropriate doses. Steroids and thalidomide in appropriate doses were used for the management of neuritis and erythema nodosum leprosum (ENL).
The study was approved by the ethics committee of the institute. Informed written consent was obtained from all patients prior to their enrollment in this study.
| Results|| |
Twenty-nine patients were included in the study, of which 19 were males. The mean age at presentation was 38 ± 17.2 years, and the mean duration of disease was 20.2 ± 18.4 months. Of the 29 patients, 17 had multibacillary leprosy and 12 had paucibacillary. Rheumatological manifestations were more common in multibacillary leprosy. The nonrheumatological manifestations of leprosy in this cohort of patients are described in [Table 1]. Overall, 22 patients had cutaneous manifestations, which included nodules, erythema nodosum, ulcers, ear lobe infiltration, acute-onset maculopapular rash, and hypoanesthetic or anesthetic macular or plaque-like patches. Thickened great auricular, ulnar and lateral popliteal nerves were seen. Lepra reactions manifested with arthritis, nodules, tenosynovitis, and/or dactylitis. NCV was done in 21 patients and revealed evidence of neuropathy, characterized either as mononeuritis or mononeuritis multiplex. One patient presented with a saddle nose, tracheal tenderness, and chondritis of the pinna with significant local tenderness, mimicking relapsing polychondritis (RP). However, both the pinna and the ear lobule were infiltrated, which distinguished it from pinna involvement of RP [Figure 1].
|Table 1: Nonrheumatological manifestations of leprosy in present cohort (n=29)|
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|Figure 1: Relapsing polychondritis-like presentation. Chondritis involving the pinna. Infiltration of the ear lobule distinguished it from chondritis in relapsing polychondritis|
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Rheumatological manifestations presented either exclusively or in combination. Various patterns of arthritis were observed in a total of 17 cases. Chronic symmetrical inflammatory small and large joint polyarthritis was most commonly observed but acute onset inflammatory polyarthritis (especially with ENL), acute/chronic oligoarthritis, especially lower limb large joint arthritis were also documented. Charcot's joint was observed in only 1 patient. No patient was initially diagnosed to have erosive arthritis. Synovial fluid examination revealed M. leprae in two patients. Three patients diagnosed to have leprosy arthritis and responded completely to MDT, subsequently redeveloped inflammatory arthritis and became significantly positive for RF and anti-CCP antibodies. They were diagnosed with RA and responded to disease-modifying antirheumatic drugs (DMARDs). Leprosy has not recurred till the last follow-up despite immunosuppressive therapy. Other manifestations seen were tenosynovitis, swollen hands, and feet syndrome (SHFS) [Figure 2] and only painful swollen feet.
|Figure 2: Swollen hand and feet syndrome are shown. Notice the arthritis of metacarpophalangeals and ankle joints with tenosynovitis|
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Fifteen patients presented with lepra reactions, most commonly ENL (n = 13). ENL was either spontaneous in onset or after initiation of MDT. ENL required prolonged therapy with steroids and thalidomide and modification of leprosy treatment. It required the addition of methotrexate in 2 patients after liver function tests settled down. Lucio phenomenon with vasculitis was observed in one patient [Figure 3].
|Figure 3: Lucio leprosy. The lower limb had patchy areas of hypoanesthesia. Cutaneous vasculitis is evident with areas of gangrene. Response to multibacillary therapy, steroids and supportive management is evident|
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The rheumatological diseases mimicked were rheumatoid arthritis (n = 10) and spondyloarthritis (n = 3), sarcoidosis (n = 2), RP (n = 1). Five patients had pure neuritic leprosy, with paresthesias and thickened nerves clinically and neuropathy on NCV. Their main presentation was either SHFS or arthritis.
The diagnostic tests performed were appropriate for the type of leprosy suspected and included slit skin smear, skin or nerve biopsy with histopathology revealing granulomatous pathology or Wade-Fite stain positive for lepra bacilli. Vasculitis was detected in one patient, and mixed septal-lobular panniculitis was seen in 2 patients. Immunological investigations revealed RF and anti-CCP positivity in low titers only; low-intensity ANA and myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibodies (ANCA) positivity were also seen [Table 2]. Radiographic changes included mild-to-moderate juxtaarticular osteopenia and joint swelling. Mild carpal crowding was occasionally observed. No definitive erosions were observed in the metacarpophalangeal (MCP), proximal interphalangeal or distal interphalangeal joints. Periosteitis was seen in a few cases (n = 5). Classical boutonniere, swan neck deformity, or gross ulnar deviation at MCPs was not observed. Other findings included a damaged joint in Charcot's arthropathy and sacroiliitis in 3 patients. The rheumatological and autoimmune manifestations seen in our cohort of patients are summarized in [Table 2].
|Table 2: Various rheumatological and autoimmune manifestations observed in leprosy (n=29)|
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The WHO guidelines were followed for treatment of these patients, as described previously. Moderate-to-high dose steroids, NSAIDs and modification of therapy was required for patients of ENL. Few patients required thalidomide. ENL responded to the addition of methotrexate in two patients. Rheumatological manifestations responded well to therapy.
| Discussion|| |
Our study exemplifies two facts: one, that rheumatological manifestations may be the presenting manifestation of leprosy and suspecting and proving the diagnosis may be a challenge for the clinician and two, rheumatological manifestations are under reported in leprosy, possibly owing to poor awareness. As observed in this study, leprosy may mimic a number of rheumatologic diseases at presentation which include RA, seronegative spondyloarthropathy (SSA), reactive arthritis, psoriatic arthritis, RS3PE, vasculitis,, sarcoidosis, RP, gout, and neuropathic joint. Further, pure neuritic leprosy and spontaneously triggered lepra reactions, pose a unique diagnostic challenge when mimicking rheumatic diseases. Tenosynovitis, pedal edema with tenosynovitis and SHFS may be clinically confused with gout, infection, reflex sympathetic dystrophy, hypoalbuminemia and renal disease, although leprosy presenting with isolated gross pedal edema is a well-recognized manifestation. The detection of autoantibodies such as RF, ANA, anti-CCP, and ANCA may further confuse the issue. Anticardiolipin antibodies have been described with increased frequency in leprosy patients.,
Lepra reactions are classified as Type I and II. Type 1 lepra reactions are characterized by exacerbation of the previously existing lesions. Patients in Type II lepra reaction develop a transient rash or erythema nodosum. Thirteen patients in the present study presented with ENL, most of them spontaneously. Overall, spontaneous ENL is considered uncommon.
In the present study, arthritis was observed in 17 and arthralgias in 3 patients. A number of these patients were on multiple DMARDs, steroids and NSAIDs but continued to have active arthritis and hence were referred to us. Atkin et al. reported predominantly Type I lepra reaction associated arthritis in 50% of their patients. They also described the chronic symmetric polyarthritis identical to RA. Cossermelli et al. described 39 cases of leprosy with arthritis not associated with lepra reaction. Pure neuritic leprosy is a well-recognized entity in India with a prevalence varying between 4.6% and 17.7%. Five patients in the present series had pure neuritic leprosy with rheumatological manifestations. They were suspected based on the presence of arthritis, paresthesias and thickened nerves. Lucio phenomenon is rarely described from the Indian subcontinent. One patient in the present study presented as vasculitis but was diagnosed to have Lucio leprosy, based on the presence of lepra bacilli in the biopsy.
Autoantibody serology in the present study (RF, Anti CCP, ANA, ANCA) was positive in low titers. This may pose a problem for the uninitiated. Once a diagnosis of leprosy has been established, these can almost always be ignored to be of no clinical significance.
[Table 3] compares the rheumatological and autoimmune manifestations seen in the present study with 3 other Indian studies.,, The study by Prasad et al. described patients presenting with rheumatological manifestations to a rheumatology outpatient department and were subsequently diagnosed to have leprosy. The study by Sarkar et al. describes 102 patients with rheumatological manifestations, of which 18 patients presented to the rheumatology clinic with arthritic manifestations while 84 patients were referred from a leprosy clinic subsequent to a diagnosis of leprosy. The present study and those by Prasad and Sarkar et al. reported inflammatory arthritis in approximately 40%–50% of cases while that by Salvi et al. reported it in approximately 85% cases. Erosive arthritis was observed by Sarkar et al. but was not reported in any of the other studies. Charcot's arthropathy was reported in the present study and that by Prasad et al. The absence of Charcot's arthropathy in other series could have been a consequence of an early diagnosis of a patient with early institution of appropriate therapy. Leprosy arthritis coexisting with RA was reported in 21% patients by Salvi et al., while RA developing after resolution of leprosy arthritis was seen in 10% patients in the present series. These patients developed significant titers of RF and anti-CCP antibodies. The coexistence of RA with leprosy arthritis or subsequent development of RA after resolution of leprosy arthritis with treatment could be a coincidental association. However, a number of hypotheses have been put forward to explain the development of arthritis in leprosy and how it could be perpetuated. Rook and Stanford have hypothesized the immunological mechanisms by which slow-growing bacteria, such as mycobacteria, may induce and perpetuate chronic arthritis. Infection with M. leprae may activate T lymphocytes in genetically susceptible individuals and lead to chronic production of lymphokines which in turn activate B lymphocytes to produce agalactosyl immunoglobulins, which perpetuate chronic inflammation and synovitis. The role of mycobacteria, specially mycobacterial heat-shock proteins, in the pathogenesis of RA has been suggested. The 65 kD heat-shock protein is an important target for arthritogenic T-cells. The perpetuation of arthritis may be a consequence of persistence of bacterial antigen inside the joint with homing of activated T-cells. More research is needed in this area.
|Table 3: Comparison of rheumatological and autoimmune manifestations reported in leprosy patients seen in a rheumatology clinic (present vs. other series)|
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A RP-like presentation of leprosy has been reported in the present series only. This manifestation needs to be borne in mind by rheumatologists, as this patient mimicked RP very closely. Lucio leprosy, considered rare in India, has been reported in all the series (one case each) except that by Sarkar et al. ENL was encountered with a similar frequency in the present series and that by Salvi et al., while there was a wide variability in the other two series. RF positivity was encountered with a similar frequency in the present series and that by Salvi et al., while it was reported in 70% of patients by Sarkar et al. The differences in reported frequencies could be a consequence of the methodology used and whether the assay was qualitative or quantitative. Anti-CCP antibodies were seen in low titers in 10% of patients in the present series, while they were not detected in the other series. There was a wide variability in the frequency of ANA positivity reported in the various series and could reflect the methodology used, variable cutoffs for positivity and interobserver variability.
Our study highlights the fact that it is not uncommon to see rheumatological manifestations in leprosy, either as part of the disease process or as the presenting manifestation of the disease. A number of rheumatological disorders may be mimicked as exemplified in the present study. A high index of suspicion, careful history, and physical examination, especially of the peripheral nerves are helpful in arriving at a diagnosis. Pure neuritic leprosy and ENL may pose special diagnostic challenges. Leprosy arthritis is a potentially treatable cause of arthritis, responding well to anti-leprosy medications and thus avoiding long and unnecessary administration of DMARDs.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]
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