MUCOCUTANEOUS
MYCOBACTERIOSIS : A SURPRISING PRESENTATION

Abstract

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Buruli
ulcer disease (caused by infection with Mycobacterium ulcerans) is the third
most common mycobacterial disease in immunocompetent people. Mycobacterium
ulcerans belongs to large group of environmental mycobacteria. Individual of
all ages are affected, but children 15 years of age or younger constitute about
75% of all cases. Spectrum of clinical disease includes nodules, plaques, edema,
characteristics skin ulcers, sometimes massive osteomyelitis. We hereby report
a case of a 38 year old man presenting with edematous and plaque like lesions
of the nose since one year followed by pus discharging sinuses in the axillary
region and was investigated on the lines of hidradenitis suppurativa and
tuberculosis. Biopsy was taken from the axillary region; histopathology of
excision biopsy revealed suppurative granulomatous inflammation but negative
for Acid-fast bacilli. Conclusive diagnosis was made only when smears from pus
discharge, scrapes were found to be highly positive for AFB, later confirmed by
culture to be of  mycobacterium ulcerans.

Introduction

The
common mucocutaneous mycobacterial infections presenting with ulceronodular lesions
are tuberculosis, leprae, mycobacterial ulcerans and others.  After tuberculosis and leprosy, Buruli ulcer
disease (caused by infection with Mycobacterium ulcerans) is the third most
common mycobacterial disease in immunocompetent people.1 Mycobacterium
ulcerans belongs to large group of environmental mycobacteria.  It is an acid-fast bacillus (AFB) with an
optimal growth temperature of 320C on routine microbiological media.2
In contrast to tuberculosis & leprosy, BU is related to environmental
factors & thus considered non-communicable. M. ulcerans infection survives
best under low oxygen tensions, such as exists in mud in the bottom of swamps.
Although the ultimate source of M. ulcerans remains obscure, the organism has
been found in aquatic insects such as water bugs, firefly larvae & beetles
in stagnant water of West Africa.3 Individual of all ages are affected,
but children 15 years of age or younger constitute about 75% of all cases.4
Today, BU is recognized as a spectrum of clinical disease that includes nodules,
plaques, edemas, characteristics skin ulcers, sometimes massive osteomyelitis.5
There is evidence that the disease may bypass the nodular stages and
disseminate contiguously in the skin. Such lesions are usually advanced when
detected & require extensive excision & skin grafting, often leading to
cosmetic disfigurement & disabling complication.2

Keywords – mucocutaneous
mycobacteriosis, buruli ulcer, atypical mycobacteria

CASE
REPORT

We hereby report a case
of a 38 year old man presenting with edematous and plaque like lesions of the nose
since one year for which the patient was diagnosed as a case of rhinophyma
(Fig. 1). After another year, he developed pus discharging sinuses in the
axillary region and was investigated on the lines of hidradenitis suppurativa
and tuberculosis. Biopsy was taken from the axillary region; histopathology of
excision biopsy revealed suppurative granulomatous inflammation but negative
for Acid-fast bacilli (Fig 3). The patient was further evaluated for
tuberculosis but there was no evidence of any other lesion elsewhere (lungs,
bones, lymph nodes) on clinico-imaging investigations. In the mean time, the
swelling of nose had spread to the adjoining face with development of ulcerated
lesions on the mucosal surface of the nose and developed ulcerative lesions in
inguinal and genital region as well (Fig 2). In view of suppurative granulomas
seen on the biopsy, antitubercular treatment was started. Induction of
anti-tubercular therapy resulted in hepatitis like syndrome with icterus,
jaundice, raised serum transaminases within 3 weeks leading to discontinuation
of therapy. Repeated pus and blood cultures (BACTEC) were found to be negative
for acid fast bacilli (AFB).  Mantoux
test was 11 mm after 72 hours. Review of earlier biopsies with further sections
confirmed the previous findings. Patient was then asked to prepare scrape
smears from the ulcerated nasal lesions. To our surprise, smears from pus
discharge, scrapes, Fine needle aspiration cytology (FNAC) smears from all the
sites were heavily positive for AFB (1% H2SO4) with suppuration and collection
of epithelioid cells in FNAC smears (Fig. 4). Tubercular serology (ELISA)
revealed IgG-664(control>225-positive) and IgM-1.0(control>1.0-positive).
In the mean time, Pus DNA-PCR turned out to be positive for Mycobacterium
tuberculosis complex. The culture for AFB came positive at 32?C.

 

DISCUSSION

 In 1948, MacCallum in
Australia was the first to isolate the etiologic agent of BU in culture from
patients. MacCallum & colleagues provisionally named this mycobacterium as
Bairnsdale bacillus, after the region where five of the six patients lived. It
was subsequently renamed Mycobacterium ulcerans.6

Despite
the increased interest in BU, the disease remained largely ignored by many national
public health programs for decades. In 1988 the World Health Organization (WHO)
recognized BU as an emerging health problem, primarily due to its frequent
disabling & stigmatizing complications.7

The
disease is endemic in rural wetlands of tropical countries of Africa’s, the
Americas, and Asia & Australia but remains uncommon in non-African
countries.8 In India there has been
no  reported case  of buruli ulcer so far to the best of our
knowledge.

Buruli ulcer
is rarely, ever, contagious. Humans become infected by traumatic introduction
of M.ulcerans into skin from the overlying M-ulcerans –contaminated surface.
M.ulcerans has an optimal growth temperature at about 32oC, but it’s
unique among mycobacteria because it produces a family of toxic macrolides, the
mycolactones, that are required for virulence.

In the
natural history of the disease, it has been observed that following traumatic
inoculation, active infection develops & causes the various manifestations
of buruli ulcer. After a few weeks or several months of active infection, progressive
necrosis of the dermis usually leads to degeneration of the epidermis &
ultimate ulceration. A necrotic slough develops in the base of the ulcer &
the surrounding skin is undermined, indurated, and hyperpigmented. Ulcers often
involve massive areas of skin.9,10,11

The infection in most instances presents as a painless lump just
under the skin. The infection is mostly on the limbs, most often on exposed
areas, but not on the hands or feet. In children, all areas may be involved,
including the face or abdomen. A more severe form of infection produces diffuse
swelling of a limb, which, unlike the papule or nodule, can be painful and
accompanied by fever.  In
the present case studied, clinically, patient presented with rhinophyma and perianal
ulceronodular lesions and within a span of two and half years there was
disseminated disease with plaques, nodules and ulceronodular lesions in the
perianal region, axilla & thighs.

Initially BU
presents as a nonulcerative lesion and can eventually evolve to ulcerative
lesions. In both types of lesion, the histopathologic sections show prominent
acellular areas of tissue necrosis with variable numbers of bacilli, usually
extracellular. Areas of inflammatory infiltrates are also seen with
intracellular M.ulcerans infection. Connor & Lunn in 1966 developed a
histopathologic classification of the disease involving 3 stages –active, organizing
(granulomatous) & healing. The active stage has the most striking and
diagnostics features, ie, contiguous coagulation necrosis of the lower dermis
& subcutaneous fat with much acid fast bacilli. The organizing stage is
seen in longstanding lesion, and is characterized by formation of granulomas.
Healing is characterized with formation of granuloma. Our biopsy was mainly in
active stage.

 For laboratory diagnosis, four methods
currently in use include 1) direct smear examination for AFB by ZN or auramine
stain, 2) in vitro culture 3) IS2404 PCR and 4) histopathologic examination.5
The most frequently available diagnostic technique is direct smear examination.
In endemic areas culture and histopathology are not easily available.  PCR can only be performed in well-equipped
laboratories. In this case smears from pus discharge, scrapes, FNACs from all
sites were heavily positive for AFB (1% H2SO4). FNAC smears showed suppuration
& collection of epithelioid cells. Repeated pus and blood cultures were
negative initially but came positive under strict temperature of 32°C.and other culture requirements Similar toMycobacterium
tuberculosis,M. ulcerans
is a member of the slow-growing group of mycobacteria. However, M. ulceransis considered extremely
slow-growing as cultures must be incubated for 6 to 8 weeks (or longer) under
appropriate laboratory conditions prior to forming distinct colonies. M. ulcerans grows optimally on
mycobacteriological media (e.g., Löwenstein-Jensen medium, Middlebrook 7H10
medium, etc.) under the same.Samples analyzed within 24 h are preferentially
kept at 4°C in a sterile vial without additive. For longer transportation
times, tissue samples should be introduced into a transport medium: Middlebrook
7H9 broth supplemented with polymyxin B, amphotericin B, nalidixic acid,
trimethoprim, and azlocillin (Becton Dickinson, Sparks, MD); oleic acid,
albumin, dextrose, and catalase (Difco Laboratories, Detroit, MI); and 0.5%
agar, also named semisolid transport medium (STM). This medium has been
recommended for use, since specimens kept in it for up to 21 days were still
culture positive.11 Primary cultures from clinical specimens are
usually positive within 6 to 12 weeks of incubation at 29 to 33°C, although
much longer incubation times of up to 9 months have been observed.12

Excised
biopsy from perianal region and axilla showed suppurative granulomatous
inflammation. The common differential diagnosis of pre-ulcerative lesions
(plaques & edematous lesion) is pyogenic cellulitis. A short trial of
treatment with antimicrobial therapy may be considered until a diagnosis of
buruli ulcer is made. Treatment options for BU include antibiotics &
surgical intervention. The choice of treatment usually based on the morphology
and extent of the lesions, as well as availability of antibiotics &
surgical facilities. Physiotherapy is imperative for all BU patients.