Tropical medicine rounds

A clinical and histopathological study of histoid leprosy

Sukumaran Pradeep Nair1, MD, and Gopinathan Nanda Kumar2, MD

1
Departments of Dermatology and
Venereology, and 2Pathology, Government
Medical College, Trivandrum, Kerala, India
Correspondence
Dr Sukumaran Pradeep Nair, MD
Department of Dermatology and
Venereology
Government Medical College Trivandrum
695011
Kerala
India
E-mail: dvmchtvm@yahoo.co.in
Conflicts of interest: None.
Abstract
Background Histoid leprosy (HL) is a rare variant of lepromatous leprosy presenting with
well-defined smooth shiny papules and nodules. This can mimic many other dermatoses
and can be missed clinically.
Methods This is a retrospective 10-year study. Data were obtained and analyzed from
case records of the urban leprosy clinic at the Government Medical College, Trivandrum,
Kerala (India).
Results There were 17 cases of HL in this study. The male/female ratio was 16 : 1 and
the 4150-year-old age group accounted for the maximum number of cases (six, 35.29%);
11 cases (64.70%) were de novo cases of HL. Papules were the commonest skin lesions
encountered (17, 100%), while the upper and lower limbs and trunk were the most
common sites involved (11, 64.70%). Earlobe infiltration was seen in 10 cases (58.82%).
Lepra reactions were seen in four (23.52%) cases. Deformity/disability occurred only in two
cases (11.76%). The mean morphological index was 30.58%, while the mean
bacteriological index was 5.17. Epidermal atrophy and a well-circumscribed dermal area
packed with spindle-shaped histiocytes and positive for acid-fast bacilli were the main
histopathological features seen.
Conclusions The majority of cases in this study were de novo. HL can occur even when
there is no history of inadequate or irregular treatment. Papules rather than nodules were
the most common skin lesions seen. Earlobe infiltration was seen in the majority of cases
unlike that reported in the literature. Lepra reactions are very rare in HL.

even by the most astute clinician.6 Therefore we decided

Introduction
Histoid leprosy (HL), first described by Wade in 1963, is
a rare variant of lepromatous leprosy (LL) presenting
with dome-shaped smooth, shiny, succulent papules
(Fig. 1) and nodules arising from an apparently normal
looking skin in contrast to LL, where the lesions arise
from infiltrated skin.1 HL was initially described in
patients who were on irregular, inadequate treatment and
dapsone monotherapy, consequently developing drug-
resistant mutant strains. Patients who had initially LL
lesions and then relapsed with histoid lesions have also
been described. However, de-novo cases of HL have also
been encountered occasionally, which are cases directly
developing histoid lesions without evidence of other types
of leprosy.2 Even though a variant of LL, this fascinating
and rare form of leprosy has ultrastructural, immunologi-
cal, clinical, and histopathological features distinct from
LL.3,4 The histoid lesions are highly bacilliferous and
hence form an important reservoir of infection of drug-
resistant mutant strains.5 Moreover HL may present with
580 localized and atypical lesions and can be misdiagnosed
to conduct this study to elucidate the clinical and histo-
pathological features of patients with HL attending the
urban leprosy clinic of this tertiary care institute.
Materials and methods
This is a 10-year (20012010) retrospective descriptive study
done in the urban leprosy clinic of the Department of
Dermatology and Venereology, Medical College Trivandrum, a
tertiary care institute. Data were collected from the case
records of patients attending the aforementioned leprosy clinic
with a diagnosis of HL. The clinical and histopathological details
of these patients were thoroughly perused from the records and
the histopathology slides reviewed. The presence of shiny skin-
colored papules and nodules arising from an apparently normal
skin were the clinical parameter for diagnosis of HL. The
duration, number of lesions, distribution, type of lesions
(macules, papules, plaques, nodules), earlobe infiltration,
presence of lepra reaction in the form of erythema nodosum
leprosum (ENL), edema of palms/soles, epistaxis, and
superciliary madarosis were the other clinical features studied.

International Journal of Dermatology 2013, 52, 580586 2013 The International Society of Dermatology
Pradeep Nair and Nanda Kumar
Figure 1 Smooth shiny succulent dome-shaped papules
arising from normal skin
The presentation with transient erythematous tender
subcutaneous nodules was the clinical parameter for diagnosis
of ENL.
Sensory impairment to temperature and touch and pain of the
skin lesions, glove and stocking type of anesthesia, peripheral
nerve thickening and presence of nerve palsies, neuropathic
plantar ulcers, and deformity were the predominant neurological
features noted. Deformities/disabilities were graded according to
WHO classification.7
Slit-skin smear for acid-fast bacilli (AFB) was done from one
earlobe, one skin lesion, and normal skin and stained by the
ZiehlNeelsen technique. Smears were examined under the oil
immersion objective for solid, fragmented, and granular forms of
AFB, and the bacterial index (BI) and morphological index (MI)
were calculated and recorded. Skin biopsy was taken from a
representative lesion and subjected to hematoxylin and eosin
stain and WadeFite stain for AFB. The presence of a well-
circumscribed collection of cells in the dermis arranged in
nodular aggregates, spindle-shaped histiocytes, and positive
staining for AFB were the histopathological parameters for
diagnosis of HL.1,8 All cases of HL clinically diagnosed and
confirmed by skin biopsy with the aforementioned
histopathological features were included in the study. The data
collected were then analyzed in terms of descriptive statistics.
Permission to conduct this study was obtained from the Human
Ethics Committee, Medical College, Trivandrum.
Results
The total number of patients analyzed in this study was
17 (n = 17). This accounted for 2.05% of the total num-
ber of new leprosy cases (17 of 829) in the study period
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Clinico-pathological study of histoid leprosy Tropical medicine rounds 581
and accounted for 16.34% of the total LL cases (17 of
104) in the study period. The salient demographic and
clinical features are given in Table 1. There were 16 men
and one woman, the male/female ratio being 16 : 1. The
age group 4150 accounted for the maximum number of
cases (six, 35.29%). The youngest was 28 years and the
oldest 75 years, the mean age being 48 years. The mean
duration of illness was approximately one year, the short-
est being two months and the longest three years. None
of the index patients had a family history of leprosy. Six
patients (35.29%) gave a previous history of treatment.
One patient (5.88%), a case of LL relapsed as HL, gave a
history of irregular treatment. Eleven (64.70%) were
de novo cases of HL, while five (29.41%) were originally
LL and one (5.88%) of indeterminate leprosy on dapsone
monotherapy, relapsed as HL. The number of lesions
ranged from 10 to 100. Papules were the predominant
lesion seen in all the patients (100%), whereas a combi-
nation of papules and nodules accounted for 15 cases
(88.23%). The upper and lower limbs and trunk were
involved in 11 cases (64.70%). One patient (5.88%) had
lesions on the palms, while none had lesions on the soles,
scalp, and mucous membrane. Six patients (35.29%) had
one or more anesthetic macules or plaques. One patient
(5.88%) had tumor-like lesions and one patient (5.88%)
had molluscum contagiosum-like lesions (Fig. 2). Earlobe
infiltration was present in 10 patients (58.82%). Four
patients (23.52%) had a type II lepra reaction in the form
of erythema nodosum leprosum (ENL) lesions. The ulnar,
common peroneal, and tibial nerves were bilaterally
thickened in all the cases. WHO grade 2 deformity/dis-
ability was present in two patients (11.76%), in the form
of left ulnar palsy in one patient (5.88%) and left plantar
ulcer in one patient (5.88%).
The bacterial smear scores and histopathological
features are given in Table 2. The MI ranged from 10
to 60% (mean 30.58%), while the BI ranged from
4.66 + to 6 + (mean 5.17). Ten patients (58.82%)
responded to classical multibacillarymultidrug treatment
(MB-MDT) with dapsone 100 mg/d, clofazimine 50 mg/
d, and a monthly pulse of rifampicin 600 mg and clofazi-
mine 300 mg. Six patients (35.29%) had ofloxacin
400 mg also added to the regimen, while one patient
(5.88%) had minocycline 100 mg added to the regimen
due to intolerance of ofloxacin.
Discussion
HL, a rare variant of LL with distinct clinical and histo-
pathological features, presents with localized smooth
shiny papules in contrast to LL, which presents with gen-
eralized symmetrical lesions. Hence, HL is often misdiag-
nosed in the clinical setting. HL is considered a rare
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582 Tropical medicine rounds Clinico-pathological study of histoid leprosy Pradeep Nair and Nanda Kumar

Table 1 Demographic and clinical features

Type of Glove and Symmetric Other

Case Age/ lesion/ stocking nerve clinical
no. sex Duration Type distribution Earlobe ENL anesthesia thickening Deformity features

1 75/M 4 months H P, N/U, L, T + Edema of

palms/soles
2 41/M 2 years H M, P, PL/U, T + + Anesthetic
macules
3 52/M 3 months H P, N/U, L, T + +
4 58/M 1 year H P, N/L, T +
5 35/M 5 months H P, N/U, L, T +
6 61/M 3 months H P/L, T + + Epistaxis
and edema
7 40/M 3 years LL-H P, N/U, L, T, Tu + +
8 47/M 8 months I-H P, N/U, L, T, +
9 30/M 2 years H M, P, PL, N/U, T + + Anesthetic
macule
10 55/M 2 years H P, PL, N/U, L T + Edema of
palms/soles
11 42/M 4 months LL-H P, PL, N/F, U, L, T + + + Left Epistaxis,
ulnar anesthetic
palsy plaques
12 43/M 8 months LL-H P, N/U, L, T + + Superciliary
madarosis
13 61/M 6 months H P, PL, N/U, L, T + Left Edema of
plantar palms/soles,
ulcer anesthetic
plaques
14 28/M 1 year LL-H M, P, N/F, U, L, T + + Anesthetic
macules
15 50/F 2 years LL-H M, P, N/U, L + + + Anesthetic
macules,
madarosis
16 51/M 6 months H P, N/F, U, T + +
17 47/M 2 months H P, N/U, L, T + + Edema of
palms/soles,
madarosis

ENL, erythema nodosum leprosum; F, face; H, de novo histoid leprosy; I-H, indeterminate leprosy relapsed as histoid; L, lower
limb; LL-H, lepromatous leprosy relapsed as histoid; M, macule; N, nodule; P, papule; PL, plaque; T, trunk; Tu, tumor-like
masses; U, upper limb.

entity. The total number of cases in this study was 17,
indicating the rarity of HL. A previous similar study by
Kaur et al.,9 had 40 cases. The incidence of HL in our
study was 2.05%. The study by Kaur et al. had an inci-
dence of 1.8%, Mendiratta et al., 1.14%, and by Kalla
et al., 2.8%, all indicating again the rarity of HL.911
The male: female ratio of 16 : 1 in this study is much
higher than the studies done by Kaur et al. (5.7 : 1) and
Sehgal and Srivastava (8.2 : 1).9,12 The 4150-year-old
age group accounting for the maximum number of cases
in this study is similar to the study by Kaur et al., and in
contrast to studies by Sehgal and Srivastava, and Kalla
et al., where the 2040-year-old age group was most
commonly affected.9,11,12 A unique highlight of this study
is the large number of de novo cases of HL (64.70%)
compared with another major study by Kaur et al.,9
where de novo cases of HL accounted for only 12.5%.
The very large number of de novo cases could be due to
them being referred to this tertiary care institute for want
of a definite diagnosis owing to the atypical presentations
of HL. The high index of suspicion maintained in this
center enabled us to pick out cases that were missed else-
where. The large number of de novo cases portrays a
grave situation as these patients are highly bacilliferous
and are infectious with drug-resistant strains. The
de novo cases could be due to single or multiple drug-
resistant strains; however, microbiological confirmation
with mouse foot pad inoculation was not possible in this

International Journal of Dermatology 2013, 52, 580586 2013 The International Society of Dermatology
Pradeep Nair and Nanda Kumar Clinico-pathological study of histoid leprosy Tropical medicine rounds 583

relapse. However, it is extremely difficult to distinguish

Figure 2 Smooth shiny papules resembling molluscum
contagiosum
institute due to lack of facilities. Contrary to literature
where inadequate, irregular treatment and dapsone mono-
therapy is implicated in the development of HL, only one
case in the present study was on dapsone monotherapy,
while one patient gave history of irregular therapy, indi-
cating other factors may be responsible for the develop-
ment of HL. All the LL relapsed cases had previously
completed the recommended MB-MDT regimen and later
relapsed as HL, thus fulfilling the WHO criteria for
clinically and by laboratory methods if these cases were
reinfected again, which is possible in endemic areas of
leprosy. The most common primary lesion seen in this
study was a papule, while in the study by Kaur et al., Ka-
lla et al., and Sehgal and Srivastava, a nodule was the
most common lesion seen.9,11,12 The most common sites
involved in this study were the upper and lower limbs
and trunk, while in the other studies the lower back,
thighs, and buttocks were the most common sites
involved.9,11,12 However, in the study by Mendiratta
et al.,10 the face was the most common site involved.
Earlobe infiltration seen in 58.82% of the cases (Fig. 3) is
a unique feature of this study as other studies mention
earlobe infiltration as a rare feature of HL.4,12 Tumor-like
masses and molluscum contagiosum-like lesions were the
atypical manifestations seen in the present study, while
xanthoma-like and mucous membrane lesions reported in
the literature were not seen in this study.6,13,14 Such atyp-
ical presentations may contribute to the misdiagnosis of
HL. The incidence of ENL in this study was low
(23.52%). Two cases of ENL occurred in LL and indeter-
minate leprosy, which had relapsed as HL, while only
two of de novo HL had ENL lesions. This shows that
ENL is very rare in de novo HL as reported in most stud-
ies.15 However, in the study done by Kaur et al.,9 the
incidence of ENL was 40%. The mean MI of 30.58%
and mean BI of 5.17 seen in this study shows the highly

Table 2 Acid-fast bacilli smear and histopathological features

Well Appendages
circumscribed Spindle- in the
Case BI MI Epidermal Grenz Pseudo- area of cells shaped circumscribed
no. (+) (%) atrophy zone capsule in the dermis histiocytes area of cells

1 5.33 60 + + + + +
2 6 30 + + + + +
3 5 40 + + + +
4 4.66 40 + + + +
5 3 10 + + + +
6 3 20 + + +
7 6 50 + + + + +
8 6 30 + + +
9 5.33 10 + + + +
10 6 15 + + + +
11 5.33 40 + + + + +
12 5 10 + + + +
13 6 40 + + +
14 6 50 + + + + +
15 5.33 20 + + + +
16 5 25 + + + +
17 5 30 + + + +

BI, bacterial index; MI, morphological index.

2013 The International Society of Dermatology International Journal of Dermatology 2013, 52, 580586
584 Tropical medicine rounds Clinico-pathological study of histoid leprosy Pradeep Nair and Nanda Kumar

Figure 4 Epidermal atrophy, Grenz zone, and circumscribed

collection of spindle-shaped histiocytes in the dermis
(hematoxylin and eosin 9100)

Figure 3 Earlobe infiltration, usually rare in histoid leprosy

bacilliferous nature of HL. The bacilli in HL are longer

and narrow with thin tapering ends (Fig. 6) compared to
the bacilli in LL, indicating they are mutant strains.3,8 A
pioneering study by Sehgal et al. and Kontochristopoulos
et al., showed augmented localized cell-mediated and
humoral immunity in the immediate vicinity of histoid
nodules compared to LL.16,17 They demonstrated
increased CD36 expression by keratinocytes, increased
CD4 cells, increased B cells, and immunoglobulins sur-
rounding the histoid nodules. This can explain localiza-
tion of the histoid nodules and the relative paucity of
AFB in perilesional skin surrounding the histoid nodule.
In spite of this, augmented local immunity fails to
increase the bactericidal activity of these cells due to the Figure 5 Cells arranged in whorls, circles, and curlicues with
antigenic effect of Mycobacterium leprae to produce sup- a few foam cells (hematoxylin and eosin 9400)
pressor cytokines.16,17
The histopathological features of HL are very specific. The pseudocapsule seen around the well-circumscribed
Epidermal atrophy, well-circumscribed collection of cells area of cells was seen in 58.82% of the cases. This occurs
in the dermis arranged in nodular aggregates (Fig. 4) due to compression of the surrounding collagen by the
composed of spindle-shaped histiocytes arranged in expansile nature of the circumscribed collection of
whorls, circles, and curlicues (Fig. 5), and with positive cells.1,3,4,8 The dermal appendages in the circumscribed
staining for AFB were the histological hallmarks in this area of cells could be seen only in two of the cases. It
study (Fig. 6). A few foam cells, which are macrophages is postulated that the high density of cells and the expan-
with vacuolated cytoplasm and peripherally displaced sile growth in the histoid nodule pushes out the der-
nuclei (Fig. 5), were observed in all the cases. This is mal appendages from the cell mass.3,8 In the present
expected as HL is basically a variant of LL.1,4,8 The well- study, similar to other studies, globi could not be
circumscribed collection of cells may show a storiform detected in the tissue specimens by AFB stain. The Myco-
pattern mimicking dermatofibroma.1,3,4,8 Even though the bacterium leprae in HL lack a matrix protein secretion
Grenz zone is mentioned in studies, in the present study it gloea, which helps in gluing the bacilli together.
could be appreciated only in 41.17% of the cases (Fig. 4). Hence, globi are not observed histologically.1,3,4,8 The

International Journal of Dermatology 2013, 52, 580586 2013 The International Society of Dermatology
Pradeep Nair and Nanda Kumar
Figure 6 Long narrow lepra bacilli with thin tapering ends
(WadeFite stain 91000)
so-called tuberculoid contamination, the presence of
epitheloid cells in the infiltrate, was not observed histo-
logically in this study.18 Tuberculoid contamination indi-
cates that the HL has relapsed from a previous higher
spectrum.
The majority of patients in this study responded to
standard WHO MB-MDT, while the remaining had
ofloxacin/minocycline added to their regimen. Studies
have shown that adding ofloxacin or pefloxacin in highly
bacilliferous cases can bring down the bacillary load
faster.19,20 In the present study, none of the patients had
immunotherapy in the form of Mycobacterium w or BCG
vaccination. Sharma et al.,21 has reported the rapid
clearance of bacilli treated with combined MDT and
Mycobacterium w vaccine.
The tendency of patients in our department to
abstain from follow-up after successful completion of
treatment permitted us to follow-up only 10 patients.
However, none of them showed evidence of relapse
even after 25 years of follow-up.
In conclusion, we would like to state that although HL is
considered a variant of LL, it has distinct clinical and histo-
pathological features. As such cases are highly bacilliferous
and probably harboring drug-resistant mutant strains, they
pose a serious threat to national elimination programs. The
large number of de novo cases, papules being the predomi-
nant lesion, the limbs and trunk being the preferred site,
and earlobe infiltration are the unique highlights of this
study. We have grave apprehensions regarding whether the
WHO-recommended fixed duration therapy for multibacil-
lary cases for one year will be sufficient to treat the highly
bacilliferous HL. Combining Mycobacterium w vaccine
with MB-MDT for HL certainly requires consideration.
Further immunological and histopathological studies in the
2013 The International Society of Dermatology
Clinico-pathological study of histoid leprosy Tropical medicine rounds 585
future may elucidate more information of this fascinating
and unique form of leprosy.
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