International Journal of Rheumatic Diseases 2012

ORIGINAL ARTICLE

Leprosy revealed in a rheumatology clinic: A case series

Shiva PRASAD,1 Ramnath MISRA,1 Amita AGGARWAL,1 Able LAWRENCE,1 Nigil
HAROON,1 Anupam WAKHLU,1,4 Narendra KRISHNANI,2 Vinita AGRAWAL,2
Vimal K. PALIWAL,3 Sanjeev JHA3 and Vikas AGARWAL1
1
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, 2Department of Pathology,
Sanjay Gandhi Postgraduate Institute of Medical Sciences, 3Department of Neurology, Sanjay Gandhi Postgraduate
Institute of Medical Sciences, and 4Department of Rheumatology, King George Medical University, Lucknow, India

Abstract
Aim: Leprosy classically presents with cutaneous and neural involvement. Rheumatological manifestations are
frequent, although often under-recognized. At times, these may present to a rheumatology clinic prior to the
diagnosis of leprosy. Herein, we present our experience with patients referred with various rheumatological dis-
orders who were subsequently diagnosed as having leprosy.
Methods: This retrospective study (January 2001–September 2010) was carried out at the Department of Clini-
cal Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, in northern India.
Patients who were confirmed as having leprosy were included. Details regarding demographic and clinical pre-
sentations were collected.
Results: Forty-four cases (30 male, mean age 40 ± 13.6 years and mean disease duration 18.7 ± 24.3 months)
were identified. Musculoskeletal manifestations included arthritis (n = 22), swollen hands and feet syndrome
(SHFS) (n = 11), tenosynovitis (n = 9), painful swollen feet (n = 9), arthralgias (n = 7) and vasculitis (n = 1).
Distribution of joints mimicked rheumatoid arthritis (n = 14) and spondyloarthropathy (n = 7). Arthritis and/
or tenosynovitis were part of spontaneous onset lepra reaction in 28 cases. Other clinical manifestations were:
paresthesias (n = 28), erythematous nodules (n = 25) and anesthetic patches (n = 7). Thirty-one patients had
thickened nerves (ulnar n = 28, common peroneal n = 21). Eight patients did not have any cutaneous manifes-
tations and had presented with SHFS and arthritis or tenosynovitis. These were labeled as pure neuritic leprosy.
Most of the patients responded to multidrug anti-leprosy therapy and glucocorticoids.
Conclusion: Rheumatological presentations of leprosy may mimic RA, spondyloarthropathy or vasculitis. Pure
neuritic variety and spontaneous type 2 lepra reaction pose unique diagnostic challenges. Increased awareness
may avoid delay in diagnosis.
Key words: arthritis, lepra reaction, leprosy, pure neuritic leprosy, swollen hand foot syndrome, tenosynovitis.

INTRODUCTION ous and neural involvement. Although musculoskeletal

Leprosy is a chronic granulomatous disease caused by
Mycobacterium leprae. It classically presents with cutane-
Correspondence: Dr Vikas Agarwal, Department of Clinical
Immunology, Sanjay Gandhi Postgraduate Institute of Medical
Sciences, Lucknow, India.
Email: vikasagr@sgpgi.ac.in
involvement has been described as the third most
common organ system involved, it has been under-
recognized and under-reported. Recently, leprosy has
re-emerged in the developed world, especially in
patients who have received anti-tumor necrosis factor a
(anti-TNF-a) agents.1,2 Moreover, increasing global
travel and migration of people from the developing
world to the developed world, has made it necessary for

© 2012 The Authors

International Journal of Rheumatic Diseases
© 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
S. Prasad et al.
physicians working in developed countries, especially
the United Kingdom, those in North America, parts of
Europe and in Australia, to be aware of the rheumato-
logical manifestation of leprosy as it may mimic various
rheumatological disorders and lead to erroneous diag-
nosis and treatment.
The prevalence of arthritis in leprosy varies from 1%
to 78%, depending upon geographical area and the
reporting center.3–5 In one of the largest studies from
India having 2500 patients with leprosy, only 27
(1.2%) had articular involvement.6 Smaller studies
from South America reported arthritis in 12/44
patients,7 whereas a study from Pakistan found arthritis
in 12/31 patients.8 However, Alcocer et al. found arthri-
tis in 12/18 (78%).9 Nearly one-third of the 66 consec-
utive leprosy outpatients seen by Atkin et al. had an
inflammatory arthritis.4 Two recent Indian studies
observed the prevalence rates for arthritis in leprosy as
61.4% and 10%, respectively.10,11 A recent study from
South America reported a prevalence rate of 6.3% in a
cohort of 1257 patients with leprosy.12
According to the World health Organization, India
has the highest incidence and prevalence of leprosy in
the world.13 Since musculoskeletal symptoms may be
the presenting manifestation of leprosy, it is important
to recognize the rheumatic manifestations of leprosy
for early diagnosis and treatment. At times, rheumatic
manifestations may present before the diagnosis of lep-
rosy is made and patients may present directly to the
rheumatology clinic. Such cases are often misdiagnosed
as various inflammatory rheumatological disorders. In
this study we present our experience of patients with
various rheumatological manifestations who presented
to our unit as connective tissue diseases and subse-
quently these patients were confirmed to have leprosy.
Their musculoskeletal manifestations improved after
therapy for leprosy.
MATERIALS AND METHODS
This retrospective study (January 2001–September
2010) was carried out at the Department of Clinical
Immunology, Sanjay Gandhi Postgraduate Institute of
Medical Sciences, Lucknow, a tertiary care referral hos-
pital in northern India. Case records of patients who
were referred to our unit with rheumatological manifes-
tations and were later diagnosed as having leprosy were
analyzed for demographic and clinical presentations.
Diagnosis was confirmed by demonstration of Mycobac-
terium leprae by slit skin smear or diagnostic histopa-
thology of skin or nerves.
2 International Journal of Rheumatic Diseases 2012
RESULTS
There were 44 patients with a male-to-female ratio of
2 : 1 and mean age of 40 years (range 16–71) and
mean disease duration of 1.5 years (range 15 days to
10 years). Thirty-six patients had cutaneous manifesta-
tions; acute onset remitting-relapsing erythematous rash
(n = 31), nodules (n = 25), ear lobe infiltrations
(n = 11), hypo/anesthetic patches (n = 7) and cutane-
ous ulcers (n = 1). Paresthesias were reported by 28,
whereas thickened nerves were present in 31 patients.
Ulnar and common peroneal nerves (CPN) were com-
monly involved (Table 1). Clinical motor weakness
was observed in four patients and two patients had claw
hand, but none had foot or wrist drop. Electrophysiol-
ogy data were available in 21 patients and showed evi-
dence of neuropathy in 17 patients (Table 1). One
patient each had, saddle nose deformity, orchitis and
iritis.
Musculoskeletal manifestations were as follows: 22
patients presented with arthritis; 14 had acute onset,
persistent, symmetric polyarthritis, involving large and
small joints with early morning stiffness of more than
half an hour; seven had lower limb predominant asym-
metric oligoarticular arthritis involving knee and ankles;
one had Charcot’s arthropathy; arthralgia was present
in seven patients; 11 presented as swollen hands and
feet syndrome (SHFS); and nine each had tenosynovitis
and swollen feet only. Eight patients had past histories
of leprosy that were treated adequately; however, they
had not received multi-drug therapy (MDT) over the
preceding 6 months. None of the patient had erosive
arthritis on radiography.
Of 44 patients, 28 were diagnosed as erythema nodo-
sum leprosum (ENL), while lepromatous leprosy was
seen in four patients, residual neuropathy in two,
Table 1 Neurological involvement in leprosy
Parameters No. of patients (%)
Paresthesias 28 (63.6)
Nerve thickening 31 (70.4)
Ulnar 28 (63.6)
CPN 21 (47.7)
Radial 4 (8.8)
Supraclavicular 3 (6.6)
Greater auricular 3 (6.6)
Facial 1 (2.2)
NCV 21 (47.7)
Neuropathy 17 (38.6)
Normal 4 (8.8)
CPN, common peroneal nerve; NCV, nerve conduction velocity.

Charcot’s arthritis and Lucio phenomenon in one each
(Table 2). All patients in lepra reaction had spontane-
ous onset reactions.
Eight patients in the present study did not have any
skin lesion at initial presentation or during follow-up.
They were diagnosed as pure neuritic leprosy. Five of
these cases have been described earlier.14 These patients
had presented with tenosynovitis (n = 3), SHFS +
arthritis (n = 2), and one each had only arthritis, SHFS,
and a combination of tenosynovitis, SHFS and arthritis.
All these patients had paresthesias or had neuropathy
on electrophysiology.
Diagnosis was confirmed by positive slit skin smear
(n = 16) and histopathology revealing M. leprae or
granulomatous pathology in skin (n = 20) or sural
nerve (n = 10) tissue. Wade-Fite stain revealing lepra
bacilli was positive in 11 skin biopsies and five nerve
biopsies. In the rest, granulomas negative for other
acid fast bacilli and fungal hyphae were found. Skin
biopsy also revealed vasculitis in three and septal
panniculitis in one patient. Serology for rheumatoid
factor (RF) was positive in two, antinuclear antibod-
ies (ANA) and antineutrophil cytoplasmic antibodies
(ANCA) in one each. Antibodies to phenolic glyco-
lipid-1 (PGL-1) was not tested due to non-availability
at our center.
Radiographs of the patients presenting with arthritis
(n = 22) revealed para-articular soft tissue swellings
(n = 14), mild juxta-articular osteopenia around the
metacarpophalangeal and proximal interphalangeal
joints (n = 12), normal bones and joints (n = 9) and
marked destruction of joints with subluxation of bones
and gross deformities in one case. None of the radio-
graphs had erosions or deformities typical of RA.
Table 2 Summary of types of leprosy and their manifesta-
tions
Parameters No. of patients (%)
Erythema nodosum leprosum 28 (63.6%)
Pure neuritic leprosy 8 (18.1%)
Tenosynovitis 3
Arthritis + SHFS 2 reaction. Type 1 lepra reaction usually manifests with
Arthritis 1 exacerbation of the previously existing lesions.16 How-
SHFS 1 ever, patients in type 2 lepra reaction have transient
SHFS + arthritis + tenosynovitis 1 rash or erythema nodosum. In the present study, 72%
Lepromatous leprosy 4 (8.8%)
Residual neuropathy 2 (4.4%)
Lucio phenomenon 1 (2.2%)
Charcot’s joints 1 (2.2%)
SHFS, swollen hands and feet syndrome.
International Journal of Rheumatic Diseases 2012
Leprosy revealed in a rheumatology clinic
Therapy and outcome
All patients except a patient with Charcot’s arthropathy
were treated with multidrug therapy according to WHO
guidelines.15 Thirty-one patients required moderate to
high doses of glucocorticoids for 3–6 months. Sixty per-
cent (n = 26) of the patients completed the treatment
regimen and completely recovered from their musculo-
skeletal symptoms. The rest of the patients were referred
to a local district leprosy center for further therapy and
did not come for follow-up. Three patients required
thalidomide for control of ENL. Relapse of skin and
musculoskeletal symptoms was observed in 15% of
cases (n = 4); however, all of them responded to
re-institution of the MDT with glucocorticoids.
DISCUSSION
It is easy to attribute rheumatological manifestations to
leprosy in a known patient with the disease; however,
suspecting and proving the diagnosis of leprosy in a
patient presenting with predominantly rheumatological
manifestations is most challenging. Our data empha-
sizes the fact that rheumatological manifestations may
be the presenting feature of the leprosy and may mimic
RA, spondyloarthropathy and/or systemic vasculitis.
Moreover, pure neuritic leprosy with musculoskeletal
manifestations and spontaneously triggered lepra reac-
tions pose a unique diagnostic challenge. Rheumatoid
factor and ANA positivity may further add to the confu-
sion in diagnosing leprosy. Failure to identify and inter-
pret paraethesias in a patient with arthritis and lack of
detailed sensory nervous system examination may delay
the diagnosis.
Hypoanesthetic/anesthetic, hypopigmented anhidrot-
ic skin lesions are the classical dermatological mani-
festations of leprosy. Patients presenting with
predominant rheumatological features in the absence
of classic dermatological manifestations are difficult to
diagnose. Rheumatological manifestations of leprosy
involve skin, articular and soft tissues. Dermatological
manifestations of lepra reactions depend on the type of
of patients presented with remitting and relapsing
rashes and 63% had nodular rashes suggestive of ery-
thema nodosum. None of the patients were on anti-
leprosy drugs, suggesting that all these patients had
spontaneous type 2 lepra reaction, compounding the
3
S. Prasad et al.
diagnostic dilemma. Spontaneous reactions considered
to be uncommon have been described in a series of 32
patients presenting for the first time. Twenty-two (69%)
patients had lepra type 2 reaction in this series.17
In present study, 50% (n = 22) of patients had arthri-
tis at presentation, 14 (32%) presenting with acute
onset persisting arthritis involving large and small
joints mimicking RA. Oligoarticular involvement like
spondyloarthropathy was seen in seven patients (16%).
All these patients were referred to our unit as refractory
rheumatoid arthritis and were on multiple disease-
modifying antirheumatic drugs (DMARDs). Lele et al.
and Modi et al. described acute onset symmetric polyar-
thritis mimicking RA during lepra reactions.6,18 Modi
et al. reported that out of 21 cases in their series, 10
had non-specific synovitis, nine had healed scarred
lesions and four had M. leprae infiltration in the synovi-
um.6,18 Gibson et al. reported the presence of arthritis
in 20 out of 31 (65%) patients with lepra reaction.9
Atkin et al. reported predominantly type 1 lepra reac-
tion associated arthritis in 19 (50%) patients in their
series of 38 patients.4 Arthritis predominantly involved
the small joints of hands and resolved by 4 weeks in
most patients.18 Atkin et al. were the first to describe
chronic symmetric polyarthritis identical to RA, not
associated with lepra reactions in leprosy patients.19
They reported 31 leprosy patients with chronic symmet-
ric polyarthritis who did not have any evidence of reac-
tional states. Cossermelli et al. described 39 cases of
leprosy with arthritis not associated with lepra reac-
tion.7 Arthritis in most of the patients was chronic
(mean duration 11 years) and RA-like in distribution.
Another unique presentation is the pure neuritic type
of leprosy.14 In the present series, 18% of patients had
the pure neuritic type of leprosy. The presence of arthri-
tis, soft tissue involvement, history of paresthesias and
thickened peripheral nerves provided the clue for the
diagnosis. A combination of arthritis, tenosynovitis
with or without paresthesias or thickened nerves is
highly suggestive of leprosy. In India, pure neuritic lep-
rosy is a well-recognized form of leprosy and its preva-
lence varies from 4.6% in northern India to 17.7% in
southern India.20,21
Despite being an endemic zone, Lucio phenomenon
is rarely described from India.22 We had one patient
with Lucio leprosy. He presented with nodulo-ulcera-
tive cutaneous lesions (Fig. 1) which were initially
thought to be vasculitis; later biopsy of the ulcer dem-
onstrated lepra bacilli in the endothelium. Soft tissue
involvement in the form of tenosynovitis, acute onset
painful edema of hand and foot with marked restriction
4 International Journal of Rheumatic Diseases 2012
Figure 1 Ulcerative lesions on the left leg anterior aspect in a
patient with Lucio leprosy.
of movements and nodules along the extensor tendons
has been described previously but is less recognized.23
SHFS was described as early as 19805 and recently by
Agarwal et al. as well.24 SHFS, swollen foot alone and
tenosynovitis were observed in patients with lepra reac-
tions and also in pure neuritic type of leprosy.
Serology for RF and other autoantibodies did not
pose a diagnostic dilemma in the present study. Both
RF+ and ANA+ patients had low titer positivity and
patients with positive ANCA serology had negative
results for anti-myeloperoxidase or anti-proteinase 3
antibodies, It is likely that this ANCA positivity was due
to reactivity with other neutrophil enzymes than the
two most common known determinants, that is, mye-
loperoxidase or proteinase-3.
Treatment with MDT and glucocorticoids led to reso-
lution of fever and joint symptoms in all the patients
followed up at our unit. Only three patients required
thalidomide and four patients had a relapse following
completion of the MDT. However, all relapsed cases
responded once MDT with glucocorticoids was
restarted.
CONCLUSIONS
Recognition of the infective agent as an etiological fac-
tor in rheumatic manifestations is important in man-
agement. Absence of classic cutaneous lesions should
not deter against diagnosing leprosy. Recognition of
rheumatological manifestations of leprosy is important
as it can be the first manifestation and can be triggered
by spontaneous lepra reactions. It may mimic RA,
seronegative spondyloarthropathy or vasculitis. History

of paresthesias, careful examination for nerve thicken-
ing and subclinical neurophysiological abnormalities
are important clues to diagnose pure neuritic leprosy.
CONFLICT OF INTEREST
We declare no conflict of interest.
KEY MESSAGE
1 Musculoskeletal manifestations could be the present-
ing features of leprosy and may mimic RA or spond-
yloarthropathies or vasculitis.
2 Pure neuritic leprosy and spontaneously triggered
lepra reactions pose unique diagnostic challenges.
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