International Journal of Rheumatic Diseases 2016; 19: 941–945
EDITORIAL REVIEW
Leprosy in the rheumatology clinic: an update on this great
mimic
Leprosy is a chronic granulomatous infection caused by
Mycobacterium leprae. The first description of the disease
dates back to the 6th century BC by Indian surgeon Sus-
hruta. The invasion of Asia by the armies of Alexander
the Great saw the spread of the disease across Europe.
Leprosy now remains endemic predominantly in the
developing world, with pockets of high prevalence
identified in Brazil, Indonesia and India (South-east
Asia [SEA]). Together, these three countries account for
80% of all newly registered cases.1 Although the num-
ber of new cases detected globally has been on the
declining trend, it remains a major problem in some of
developing countries. Improved connectivity across the
continents has led to increasing global travel, and case
reports of this disease amongst the migrants have sur-
faced in developed nations as well. These are likely to
be missed by unaware physicians. The use of newer
immunosuppressants, anti-tumor necrosis factor in par-
ticular, have also been associated with reports of
leprosy.2 Early diagnosis and full course of treatment
are critical for prevention of lifelong neuropathy and
disability in these cases.
Although a vast majority of cases manifest with der-
matologic and neurologic features, musculoskeletal
manifestation are also quite common. The prevalence
of rheumatic manifestations in leprosy varies across case
series, ranging from 1–2% described in large dermatol-
ogy series to 60–80% from rheumatology clinics.3–5
This wide variability in the reported prevalence suggests
that documentation of rheumatologic signs and symp-
toms depends on the specialty in which the patient is
being treated, and rheumatic manifestations of leprosy
as a whole is often under-reported by non-rheumatol-
ogy services. Therefore, it is a felt need for awareness of
the condition among rheumatologists, as joint involve-
ment can be the only manifestation in some cases.
EPIDEMIOLOGY
The World Health Organization (WHO) achieved the
elimination of leprosy as a public health problem
© 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd
(prevalence less than one case per 10 000 persons)
globally in the year 2000. The prevalence rate of leprosy
has dropped by 99% from 21.1 per 10 000 in 1983 to
0.24 per 10 000 in 2014. The annual leprosy statistics
in 2015 from 121 countries indicate that leprosy still
exists at least in small numbers of cases in many coun-
tries. In 2014, 213 899 new cases were reported in the
world; 94% of these were from 13 high endemic coun-
tries, with the remaining 6% of new cases from the 108
other countries.6 The leprosy control program now
aims to focus on the 13 most highly endemic countries
in order to achieve its targets. Most of these endemic
countries belong to SEA and Central America.
Lepromatous manifestations are most often seen in
males across all series. These are more common in peo-
ple from rural areas although some studies have found
equal prevalence in rural and urban areas. Although
rheumatologic manifestations can be seen in all types
of leprosy, these are more common in the lepromatous
variety.
CLINICAL FEATURES
The classic manifestations of leprosy vary from macules
to plaques and nodules, which are often hypo-pigmen-
ted or hypo-anesthetic. Neurologic manifestations can
range from mononeuropathy to mononeuritis multi-
plex and distal symmetric polyneuropathy.
Charcot’s arthropathy is the classic rheumatologic
manifestation of leprosy often described in textbooks; it
is usually seen in long-standing cases with neurologic
involvement. Ankle and knee are most commonly
involved. Findings may range from subluxation, dislo-
cation or pathologic fractures to complete joint destruc-
tion. Although it is deemed to be prevalent in one in 10
cases, data from rheumatology units has yielded a sur-
prisingly lower number.7 This change could also be
attributable to the early and widespread use of mul-
tidrug therapy (MDT). Interestingly, a plethora of
rheumatologic phenomena may be uncovered in a host
with poor immunity after the initiation of MDT.
Editorial Review
Acute symmetric polyarthritis in leprosy is often
explosive in onset and associated with Lepra reaction.
Small joints of the hands and feet are most commonly
involved, although knees and elbows can be affected.
These usually last for a few weeks and resolve com-
pletely with treatment, although recurrences have been
described.8
Leprosy can also have chronic polyarthritis resem-
bling rheumatoid arthritis (RA). Atkin et al.9 were the
first to describe such presentations in the absence of
Lepra reaction. Messina et al. have described similar
manifestations in 39 cases. The mean duration of arthri-
tis in their patients was 11 years, and most had erosive
disease with classic hand deformities, making differenti-
ation from RA difficult.10 Chopra et al. have also
described seven cases of leprosy with coexistent RA.11
Prasad et al. have described articular manifestations
akin to spondyloarthropathy (spA). In that study, one-
third of those with arthritic manifestation had asym-
metric lower limb oligoarthritis.12 Sacroiliitis is not a
common manifestation, although Messina et al.10 had
an astonishing prevalence of 63% in their 55 cases.
Most had bilateral sacroiliitis, although it did not corre-
late with lower back pain. Lepromatous leprosy is the
most common subtype associated with this manifesta-
tion.
Prasad et al.12 have also reported arthritis and
tenosynovitis with or without paraesthesias or thick-
ened nerves in 18% of cases in their series. These cases
belong to pure neuritic subtypes of leprosy, as they do
not have cutaneous manifestations. Presence of thick-
ened or tender nerves may clinch the diagnosis. Ulnar
and common peroneal nerve thickening should always
be looked for; at times the radial, supraclavicular, grater
auricular and facial nerves can also be thickened.12 At
times, patients present with only tenosynovitis in the
form of swollen hands and feet syndrome (SHFS). A
series from Argentina has described up to 66% preva-
lence of this manifestation in their patients.13 This may
be a feature of pure neuritic leprosy, or less commonly
a part of generalized Lepra reaction.
Leprosy may mimic vasculitis at times. This happens
in cases with high bacillary load where the vascular
endothelium is teeming with bacilli. Popularly known
as ‘lucio leprosy’, as ‘lucio’ means beautiful in Mexican,
the skin of the patient is diffusely infiltrated so the nat-
ural wrinkles are obliterated, imparting a shiny hue.
This variety is extremely rare in Asia, most cases being
described from Mexico and Costa Rica. It is one of the
most severe forms of leprosy and can be fatal at
times.14 Albeit rare, cryoglobulinemia can be another
942
cause for vasculitis in a leprosy patient without lucio
phenomenon. Although cryoglobulins have been
described in up to 40% of leprosy cases, vasculitis is
rare and limited to case reports. The cryoglobulins in
these cases are polyclonal immunoglobulin G (IgG)
and IgM.15 In the present issue of this Journal, Dionelle
and colleagues from Malaysia have described a case of
an elderly man presenting with painful neuritis and
fingertip ulcers mimicking systemic necrotizing vasculi-
tis. It is of note that laboratory workup was inconclu-
sive; however, careful clinical examination revealed
indurated hypoaesthetic plaques and nerve thickening
followed by skin biopsy which clinched the diagnosis
of paucibacillary leprosy. It is to be noted that Malaysia
is a non-endemic zone for leprosy.16
Leprosy is a great masquerader and true to this name,
varied manifestations resembling different connective
tissue diseases have been described in this infectious
disease. Biopsy-proven cases of leprosy can present with
heliotrope rash, muscle weakness and elevated muscle
enzymes, oral ulcers, malar rash and photosensitivity,
or a picture completely resembling scleroderma with
Raynaud’s phenomena, pitting scars and skin thicken-
ing.17,18 In another case series, Danda and colleagues
reported three patients with Lepra reaction presenting
as arthritis, lupus-like and polyarteritis nodosa-like dis-
ease, respectively.19
Reactional states are systemic inflammatory compli-
cations arising from immunologic phenomenon, seen
in 30–50% of all leprosy patients.20 Type 1 Lepra reac-
tion most commonly affects patients with borderline
disease and is called upgrading reaction when induced
by anti-lepromatous therapy. Rarely, it can signify dete-
rioration in patient’s immunity when it occurs sponta-
neously; it is then called downgrading reaction. Type 2
Lepra reactions on the other hand, affect lepromatous
leprosy (LL) patients or those with borderline leprosy
(BL). It is also called erythema nodosum leprosum
(ENL). Type 1 reaction is characterized by new inflam-
mation in pre-existing skin lesions marked by erythema
and induration. SHFS and ulcerated skin lesions have
also been described. Neuritis is marked by pain and
tenderness in one or more nerves. It can result in severe
nerve injury if not treated early. A type 2 reaction is
marked by the sudden appearance of numerous painful
nodules due to panniculitis. Some of these lesions can
ulcerate and exude pus. The patients with ENL look ill;
they usually have high fever, lymphadenopathy, orchi-
tis, iridocyclitis, muscle tenderness and arthritis. The
natural course of the condition is 1–2 weeks, but recur-
rences are common. ENL has been more commonly
International Journal of Rheumatic Diseases 2016; 19: 941–945

described from rheumatology units than type 1 reac-
tion.11,12
EVALUATION
Demonstration of acid-fast bacilli (AFB) in the dermis
forms the cornerstone of diagnosis. Patients with
good immunity (tuberculoid end of spectrum)
usually have well-developed granulomas and may not
have AFB in tissues. Patients at the lepromatous end
of the spectrum have no apparent resistance to
M. leprae as seen by sheets of foaming macrophages
teeming with AFB.
Paucibacillary (PB) leprosy is defined as five or fewer
skin lesions without detectable bacilli on skin smears.
Patients with only a single skin lesion are classified sep-
arately as single-lesion PB. Multibacillary (MB) leprosy
is defined as six or more lesions and may be skin-smear
positive.21 A high index of suspicion is required for
diagnosis as leprosy closely mimics other rheumato-
logic conditions. Leprae bacilli are not always found on
investigations; hence other differentials need to be
excluded. False auto antibody positivity is another con-
founding variable, often leading to confusion in the
clinic. Most series have described rheumatoid factor
(RF) and anti-nuclear antibody (ANA) positivity in up
to one-third of all leprosy cases and two-thirds of the
lepromatous variety. False cytoplasmic positivity for
anti-neutrophil cytoplasmic antibody (ANCA) is com-
mon on immunofluorescence assay.3 Testing for anti-
proteinase 3 and myeloperoxidase by enzyme-linked
immunosorbent assay can be useful under these cir-
cumstances to rule out underlying ANCA-associated
vasculitis, as these are usually negative in leprosy.
Anticitrullinated peptide antibodies (ACPA), serology
for human immunodeficiency virus and syphilis are
usually negative.11 In an another study, except for IgA
RF, none of the serological tests showed any association
with articular manifestations in leprosy. IgA RF are gen-
erally not available in routine day-to-day clinical prac-
tice. However, ACPA antibodies are less common in
arthritis of leprosy as reported by others. This paper also
appears in this issue of IJRD.22
The gold standard for diagnosis in cases of arthritis is
demonstration of AFB in joints. It is rare to find
M. leprae in the joint fluid.18 Joint aspirates can range
from non-inflammatory to turbid effusions with high
total leukocyte count. Synovial biopsies can have vari-
able histological findings in the form of non-specific
chronic inflammation, epitheloid cells infiltration,
granulomas or AFB.
International Journal of Rheumatic Diseases 2016; 19: 941–945
Editorial Review
Radiographs of hands and feet can show specific
changes like acro-osteolysis, periosteal reaction, sub-
articular cyst, enlargement of nutrient foramina, sublux-
ation or complete joint destruction.23 Classical changes
like acro-osteolysis are seen in cases with long-standing
neuropathy. Non-specific changes such as soft tissue
swelling and generalized or juxta-articular osteopenia
are seen in almost all cases.9,10 Interestingly, most
rheumatology series have failed to demonstrate destruc-
tive changes in joints; this again raises the possibility
that rheumatologic manifestations occur before irre-
versible damage sets in.
Antibodies to phenolic glycolipid 1 (PGL-1) are more
often seen in lepromatous disease (90%) as they have
polyclonal reactivity.24 Patients with tuberculoid dis-
ease seldom produce antibodies to PGL-1 and therefore
the test is not useful for diagnosis of this subset of
patients in whom establishing the diagnosis is most dif-
ficult. Polymerase chain reaction for detection of
M. leprae DNA in tissues is still considered to be a
research tool, although it has sensitivity and specificity
of 90% and 100%, respectively.25
MANAGEMENT
Although MDT forms the cornerstone of leprosy man-
agement, presence of rheumatologic manifestations
often mandates the addition of immunosuppression.
Drug resistance in leprosy is extremely rare and failure
to improve is almost always due to poor compliance.
With the reduction in global prevalence of leprosy,
WHO26 has reduced the recommended duration of
MDT to 12 and 6 months for multibacillary and pau-
cibacillary leprosy respectively, as a cost-cutting mea-
sure. However, shorter treatment regimes have been
associated with greater incidence of relapse; hence, in
hotspots like SEA more intensive regimes may be more
appropriate. It is, therefore, recommended to continue
therapy for at least 2 years in paucibacillary leprosy and
5 years to lifelong in multibacillary leprosy.27
Neuritis must be treated aggressively to prevent or
minimize nerve injury. Nerve function improves in 60–
70% of cases with timely management. In a controlled
trial of treatment for type 1 reactions with three different
treatment regimes, greatest improvement occurred in
those receiving concurrent high-dose steroids for long
duration (prednisolone 1 mg/kg for 20 weeks or
longer).28 Prednisolone should be slowly tapered in type
1 leprae reaction once it is controlled. In general, it takes
3 and 9 months in tuberculoid and LL, respectively to
achieve optimum control. Prophylactic steroids are not
943
Editorial Review
helpful in preventing type 1 Lepra reaction. Cyclosporine
has been tried in non-responders and those with con-
traindication to steroids.29 In cases with ENL, a shorter
course may suffice, although recurrences are common on
withdrawl of cyclosporin. Tapering over 2 months may
be possible when reaction is controlled, but those who
relapse may require a longer duration of therapy. The set-
ting of chronic ENL necessitates the addition of clofaz-
imine at higher doses. Thalidomide has also been
proven effective in ENL, although neuropathy and ter-
atogenicity are limiting factors.30
Management of Lucio phenomenon requires antibi-
otics and steroids with good wound care. Anti-tumor
necrosis factor agents also have been beneficial in
refractory ENL.31
CONCLUSION
Leprosy is a great mimicker (may mimic RA, seronega-
tive SpA, lupus or systemic necrotizing vasculitis) as far
as the rheumatologic manifestations are concerned.
Even in areas of the world where leprosy is endemic,
inflammatory arthritis and other rheumatological mani-
festations due to leprosy remain underdiagnosed. Thus,
leprosy should be diligently searched in a case with
unexplained articular manifestations, especially if the
patient is hailing from endemic areas, as these may be
the first and only presenting complaint.
AUTHOR CONTRIBUTIONS
All authors had access to the data and played a role in
writing this manuscript.
FUNDING
None.
CONFLICTS OF INTEREST
None.
ACKNOWLEDGEMENTS
The authors would like to thank Professor Ramnath
Misra, Head, Department of Clinical Immunology, for
his critical inputs and valuable guidance in preparing
this manuscript.
Latika GUPTA,1Abhishek ZANWAR,1Anupam
WAKHLU2 and Vikas AGARWAL1
944
1
Department of Clinical Immunology, Sanjay Gandhi
Postgraduate Institute of Medical Sciences, and
2
Department of Rheumatology, King George Medical
University, Lucknow, India
Email: vikasagr@sgpgi.ac.in
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