Pulmonary Mycobacterium abscessus infection-induced erythema induratum

Abstract

Erythema induratum (EI) is clinically characterized by recurrent crops of tender nodules on the lower legs and lobular panniculitis with granulomatous inflammation and pathologically characterized by vasculitis and focal fat necrosis. Currently, many authors consider EI to be a multifactorial disorder with diverse causes, including Mycobacterium tuberculosis and hepatitis C infection. Here, we report a case of a 65-year-old female with a 1-year history of recurrent crops of tender nodules and plaques on her bilateral lower legs. In addition, she had suffered from a chronic cough with sputum for 1 year and had contact history with pulmonary nontuberculous mycobacterial infection from her husband. The histopathological findings of the skin biopsies were consistent with the diagnosis of EI. Chest computed tomography revealed multiple lymphadenopathy and two sets of sputum cultures showed M. abscessus. After 2 months of anti-nontuberculous mycobacterial therapy with ciprofloxacin, the skin lesions resolved completely and there was no recurrence within the following year.

Full text

CASE REPORT
Pulmonary Mycobacterium abscessus infection-induced erythema induratum
Chin-Yin Liu
1
, Horng-Shin Lin
1
, Yu-Ping Hsiao
1
, Yuan-Ti Lee
2
, Jen-Hung Yang
1
,
*
1
Department of Dermatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
2
Division of Infectious Diseases, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
article info
Article history:
Received: Jun 1, 2011
Revised: Sep 26, 2011
Accepted: Mar 12, 2012
Keywords:
erythema induratum
Mycobacterium abscessus
nontuberculous mycobacterium
abstract
Erythema induratum (EI) is clinically characterized by recurrent crops of tender nodules on the lower
legs and lobular panniculitis with granulomatous inflammation and pathologically characterized by
vasculitis and focal fat necrosis. Currently, many authors consider EI to be a multifactorial disorder with
diverse causes, including Mycobacterium tuberculosis and hepatitis C infection. Here, we report a case of
a 65-year-old female with a 1-year history of recurrent crops of tender nodules and plaques on her
bilateral lower legs. In addition, she had suffered from a chronic cough with sputum for 1 year and had
contact history with pulmonary nontuberculous mycobacterial infection from her husband. The histo-
pathological findings of the skin biopsies were consistent with the diagnosis of EI. Chest computed
tomography revealed multiple lymphadenopathy and two sets of sputum cultures showed M. abscessus.
After 2 months of anti-nontuberculous mycobacterial therapy with ciprofloxacin, the skin lesions
resolved completely and there was no recurrence within the following year.
Copyright Ó2012, Taiwanese Dermatological Association.
Published by Elsevier Taiwan LLC. All rights reserved.
Introduction
Erythema induratum (EI) was first described by Bazin in 1861 and
was considered to be related to tuberculids. Montgomery et al
introduced the term nodular vasculitis in 1945 to differentiate EI as
lesions of nontuberculous origin.
1
EI is clinically characterized by
recurrent crops of tender nodules on the lower legs, and its
pathology shows lobular panniculitis with granulomatous inflam-
mation, vasculitis, and focal fat necrosis.
Currently, many consider EI to be a multifactorial disorder with
diverse causes, including tuberculosis and hepatitis C infection.
Herein, we report a case of EI related to pulmonary Mycobacterium
abscessus infection.
Case report
A 65-year-old woman presented with a 1-year history of recurrent
crops of painful reddish nodules on both lower legs. She was
administered doxycycline at the rheumatology department, but her
skin condition did not show an evident response. The patient had
a history of chronic hepatitis B with liver cirrhosis, which was
complicated by hepatocellular carcinoma status and post-
transcatheter arterial embolization that had been performed twice
in 2008. Follow-up abdominal ultrasonography in 2010 revealed
the absence of local recurrence. Moreover, a second cancer over the
left thighdliposarcomadwas diagnosed in 2009 and successfully
treated with a wide excision.
Physical examination revealed multiple tender, reddish, and
violaceous subcutaneous nodules on the right calf and both ankles
(Figure 1). No ulceration or regional lymphadenopathy was iden-
tified. The laboratory examinations indicated elevated liver func-
tion (AST/ALT, 39/45 IU/L; normal ranges: 13e38/3e37 IU/L) and
positive antinuclear antibody (1:160, speckled type), but there
were no remarkable findings in terms of the complete blood cell
count, erythrocyte sedimentation rate, or C3 and C4 complement.
Clinically, the differential diagnosis included erythema nodosum,
nodular vasculitis/erythema induratum, polyarteritis nodosum,
and cutaneous metastasis of liposarcoma.
We performed a skin biopsy on the right ankle nodule, and the
histopathology revealed predominant lobular panniculitis with
focal lipophagic and coagulative fat necrosis. Granulomatous infil-
trations with epithelioid histiocytes, multinucleated giant cells, and
lymphocytes were present. Small- to medium-sized blood vessels
*Corresponding author. Current address: Department of Dermatology, Tzu-Chi
General Hospital, 707, Section 3, Chung Yang Road, Hualien, Taiwan, Republic of
China. Tel.: þ886 3 8565301x2001; fax: þ886 3 8573053.
E-mail address: jh1000521@gmail.com (J.-H. Yang).
Contents lists available at SciVerse ScienceDirect
Dermatologica Sinica
journal homepage: http://www.derm-sinica.com
1027-8117/$ esee front matter Copyright Ó2012, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. All rights reserved.
doi:10.1016/j.dsi.2012.03.002
DERMATOLOGICA SINICA 31 (2013) 25e27

demonstrated lymphohistiocytic infiltration and fibrinoid degen-
eration of the vessel walls (Figure 2). Neither Gomori methenamine
silver stain nor the acid-fast stain showed evidence of microor-
ganisms. Direct immunofluorescence showed IgM and C3 deposi-
tion on the small-sized vessel walls in the subcutis.
Chest X-rays revealed interstitial patterns in both lung fields.
Chest computed tomography showed multiple enlarged lymph
nodes over the right hilar, subcarinal, subaortic, and pretracheal
retrocaval spaces with focal calcification (Figure 3). Two sets of the
sputum cultures showed NTM, and M. abscessus type 1 was iden-
tified by molecular analysis using polymerase chain reaction (PCR)-
restriction fragment length polymorphism. However, the results of
the PCR and tissue culturing for M. abscessus using the biopsy
specimen were all negative. The patient was diagnosed as EI caused
by pulmonary M. abscessus infection. She was treated with twice-
daily administrations of 1 g ciprofloxacin for 2 months, which
resulted in complete resolution of the skin lesions. No recurrence
was noted at the 1-year follow-up examination.
Discussion
EI clinically presents as painless to tender, deep-seated, circum-
scribed nodules and plaques, usually on the lower legs with
a predilection for the posterior calf. Most of the lesions extend
toward the surface, become ulcerated, and heal with scarring and
atrophy. EI may be associated with erythrocyanosis, heavy column-
like calves, and cutis marmorata. It more frequently presents in
middle-aged obese women with some degree of venous insuffi-
ciency in the lower extremities and is exacerbated by cold weather.
The clinical course is often protracted and recurrent episodes can
develop over subsequent years.
The histopathology of EI is mainly lobular panniculitis that
shows granulomatous inflammation with focal necrosis, vasculitis,
and septal fibrosis with varying combinations.
1,2
However, vascu-
litis is not always identified and is not a requisite for the diagnosis.
Sequra et al found that EI can demonstrate a variety of presenta-
tions of vasculitis and that in approximately 10% of cases the
Figure 1 Multiple erythrocyanotic nodules and plaques on the right posterior calf and ankle.
Figure 2 (A) Granulomatous infiltration with lymphocytes, histiocytes, and multinucleate giant cells (hematoxylin and eosin, 100). (B) Small- to medium-sized vessel vasculitis
(hematoxylin and eosin, 200).
C.-Y. Liu et al. / Dermatologica Sinica 31 (2013) 25e2726

clinicopathological patterns of vasculitis cannot be demonstrated.
3
Thrombosis and occlusion of the lumen produce ischemic and
caseous necrosis. Extensive necrosis leads to the involvement of the
dermis, subsequent ulceration, and the discharge of liquefied
necrotic fat.
3
The histological features vary depending on the stage
of the lesion that is biopsied. Fully developed lesions show granu-
lomatous inflammatory infiltrates, epithelioid cells, foamy histio-
cytes, and either Langhans-type or foreign body-type giant cells.
The pathophysiology of EI is believed to be a hypersensitivity
reaction to a variety of antigens and immune complexes.
M. tuberculosis is considered to be the etiological factor for EI,
especially in M. tuberculosis endemic areas.
4,5
PCR indicates the
presence of M. tuberculosis DNA in approximately 50% of skin
lesions, and the pathological findings for EI are consistent in
Taiwan.
6
Bayer-Garner et al examined their EI patients for non-
tuberculous mycobacterium DNA using PCR, but the results were
negative, as in our case.
10
The negative result of PCR may be due to
a hypersensitivity reaction. Recently, hepatitis C virus has also been
suggested as a possible causative agent, and this association is
probably mediated by circulating immune complexes.
7e9
However,
the etiology can only be identified in a small proportion of EI
patients.
M. abscessus has been ranked as one of the top five most
frequently isolated mycobacterial species in Taiwan and is classified
as a rapidly growing, Runyon group IV mycobacterium. It is
distributed worldwide and is found in soil, natural and processed
water sources, and medical devices. M. abscessus causes a wide
range of clinical diseases, including skin and soft tissue infection,
keratitis, osteomyelitis, pulmonary infection, and disseminated
infection. In skin and soft tissue infections, it usually follows pene-
trating trauma and typically occurs in immunocompetent individ-
uals. The clinical presentation ranges from asymptomatic to tender
erythematous nodules and plaques, cellulitis, abscesses, ulcers, and
draining sinus with serosanguinous discharge. The lesions may be
solitary or multiple, and localized lymphadenopathy is occasionally
seen.
11
In addition, nontuberculous mycobacteria has been reported
in associated with Sweet’s syndrome, but these reports are quite
rare.
12
Until now, only 18 cases have been reported in the English
medical literature and 11 of these were caused by M. abscessus
infection. The drugs used to treat M. abscessus infections include
cefoxitin, imipenem, minocycline, doxycycline, clarithromycin,
amikacin, tigecycline, and ciprofloxacin; generally, these drugs are
administered in combinations of at least two drugs in order to
prevent resistance.
11
Our patient was an immunocompromised host with hepatocel-
lular carcinoma, liposarcoma, and was susceptible to atypical
mycobacterium infection. She suffered from chronic cough
with sputum for 1 year and had a contact history of exposure to
pulmonary nontuberculous mycobacterial infection. Chest
computed tomography revealed multiple mediastinal lymphade-
nopathies, and two sets of the sputum cultures and molecular
analysis indicated M. abscessus. Based on the clinical presentation
and the imaging and microbiological studies, the diagnosis for this
patient was pulmonary M. abscessus infection. The patient was
treated with ciprofloxacin, and the skin manifestations regressed
within 2 months. The abovementioned findings supported the
diagnosis of EI caused by pulmonary M. abscessus infection,
although the M. abscessus DNA-PCR examination of the skin lesion
produced a negative result.
To the best of our knowledge,this is the first documented case of
EI caused by M. abscessus lung infection, and it was successfully
treated with ciprofloxacin. We hope our experience can be of help
to physicians and patients faced with this disorder.
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Figure 3 (A) Chest radiographic image revealing increased density in the retrocardiac region and increased infiltration in both lung fields. (B) Chest computed tomography revealing
retrocaval, right hilar, and subcarinal lymphadenopathies (white arrows).
C.-Y. Liu et al. / Dermatologica Sinica 31 (2013) 25e27 27