Advances in Infectious Diseases, 2013, 3, 295-299
Published Online December 2013 (
Open Access AID
Tenosynovitis and Sporotrichoid Disease Due to M.
marinum on a Patien t u n d e r A n t i - TNFα Therapy*#
Diana Póvoas, J. Machado, F. Maltez
Hospital de Curry Cabral, Centro Hospitalar de Lisboa Central, EPE, Lisboa, Portugal.
Received September 26th, 2013; revised October 26th, 2013; accepted November 4th, 2013
Copyright © 2013 Diana Póvoas et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
There have been several reports of tuberculosis (TB) and, less frequently, of nontuberculous mycobacterial (NTM) in-
fections in association with tumor necrosis factor α inhibitor (anti-TNFα) therapy. Mycobacterium marinum is a NTM
with a distinct epidemiology and is infrequently responsible for disease in humans. Most commonly, it causes localized
skin infections, but in 20% to 40% of cases, it involves deeper structures. Disseminated disease is exceptional and has
been reported to occur only in immunocompromised patients. The authors report a clinical case of tenosynovitis and
sporotrichoid disease due to M. marinum in a 45-year-old male patient under anti-TNFα therapies for spondyloarthro-
pathy. Along antimicrobial therapy, the patient underwent surgical debridement and after two years he is still on treat-
ment but substantially improved. A few cases of M. marinum infection occurring in patients treated with anti-TNFα
drugs have been reported. The diagnosis of infection due to M. marinum requires a high index of suspicion from a
properly obtained exposure history and is important so that efficient diagnostic approach and treatment are ensured.
Keywords: Mycobacterium marinum; Anti-TNFα Drugs
1. Introduction
Human infection due to Mycobacterium marinum was
reported as a tuberculoid infection and historically recog-
nized in people using public swimming pool. Most infec-
tions occur after contact with contaminated water from
“swimming pool” or “fish tank”, most frequently after
minor abrasion, laceration, puncture or bite wounds. Hu-
man infections with M. marinum are localized primarily
to the skin; most commonly, M. marinum presents as a
solitary papulonodular lesion on a finger or hand, and in
some cases, it takes on a “sporotrichoid” form with one
or more nodules in the proximal skin along paths of pre-
sumed lymphatic spread. Deep infections such as teno-
synovitis (the most frequent), osteomyelitis, arthritis and
bursitis occur in 20% to 40% of cases. A few cases of M.
marinum in patients treated with anti-TNFα therapy have
been reported.
2. Clinical Case
On December 2008, a 45-year-old white man, with a pre-
vious history of spondyloarthropathy, with long lasting
complaints of articular inflammatory pain on the elbows,
shoulders, hip and knees treated with non-steroidal anti-
inflammatory drugs (NSAIDs), developed two papulo-
nodular erythematous lesions on the second and the third
finger of the right hand (Figure 1). He was responsible
for the maintenance of his domestic fish tank.
Although he had no recollection of trauma, he exhib-
ited a puncture-like wound on his right thumb. He was
medicated with flucloxacillin. On the following six
months, the papulonodular lesions remained the same but
since he reported worsening of articular complaints on
the right hand, local injection with corticosteroid was
done, without improvement. Later, he had worsening of
his spondyloarthropathy refractory to conventional ther-
apy, so he was started on etanercept after two months of
isoniazid due to positivity of both purified protein de-
rivative (PPD) tuberculin skin testing and gamma inter-
*Statements: All persons gave their informed consent and authorized
ublication of this case report. All authors declare that the submitted
work has not been published before (neither in English nor in any other
language) and that the work is not under consideration for publication
#Conflict of interest: On behalf of all authors, the corresponding autho
states that there is no conflict of interest.
Corresponding author.
Tenosynovitis and Sporotrichoid Disease Due to M. Marinum on a Patient under Anti-TNFα Therapy
Figure 1. Initial papulonodular lesion.
feron release assay (IGRA). About ten months later,
there was intensification of the swelling and redness of
the second and the third finger of the right hand, along
with worsening pain and functional limitation. Etanercept
was stopped and he was started on adalimumab. The
hand lesions evolved to tenosynovitis and the patient un-
derwent synovectomy of the hand and fingers on Novem-
ber 2010, six weeks after adalimumab was stopped (Fig-
ure 2). Acid-fast bacilli were seen in the histological tis-
sue surgically removed and M. marinum grew in the cul-
ture of tissue. The susceptibility testing showed M. ma-
rinum sensible to rifampin, ethambutol, clarithromycin
and amikacin.
About eleven months later treatment with rifampin,
ethambutol and clarithromycin was started, he developed
multiple cutaneous nodular lesions of the right arm, some
with pus-draining fistulae (Figure 3). He underwent a se-
cond surgery, with division of the muscle, tendon and
hand fascia. After 2 years, the patient is still on treatment
(with minocycline) but he has significantly improved.
3. Discussion
The incidence of nontuberculous mycobacteria (NTM)
associated disease has increased markedly in the last de-
cades, mostly due to the advent of the AIDS epidemic
and the introduction of immunosuppressive therapies [1].
Infection or reactivation of M. tuberculosis and atypical
mycobacteria has been documented as a risk of tumor
necrosis factor α inhibitor (anti-TNFα) therapy [2,3].
Almost all NTM can cause cutaneous disease, the most
common species in the USA and Europe being M. mari-
num and M. ulcerans, and the rapidly growing mycobac-
teria (RGM) M. abscessus, M. fortuitum and M. chelonae
[1,4-7]. Immunosuppression seems to be an important
risk factor in the development of lesions due to these
agents, with the possibility of deep tissue invasion, even
in the absence of previous skin trauma [1]. In the case
described, even though the patient presented what could
be interpreted as a puncture-like wound, he had no mem-
ory of preceding skin injury of the hand.
M. marinum was first isolated in 1951 from a patient
(a) (b)
(c) (d)
(e) (f)
Figure 2. (a)-(g) progression after synovectomy, with deep
tissue exposure.
with a “swimming pool granuloma” and since then, M.
marinum infections have occurred after contact with con-
taminated water from swimming pools and home aquari-
ums [8]. However, M. marinum infections are rare and
their incidence was recently estimated to be less than 1
case per 100,000 inhabitants per year [9].
Similarly to the lesion developed initially by our pa-
tient, M. marinum infection is usually a cutaneous dis-
ease characterized by a solitary papulonodular lesion on
a finger or hand or a suppurating abscess at the site of
trauma, but patients often do not seek medical attention
until symptoms become more florid [10]. Frequently, the
clinical course is indolent, with delayed presentation and
diagnosis occurring after several months. In some studies,
the mean delay in presentation was 4.9 (0.3 - 120)
months [10] and 7.7 (range, 1 - 36) months [11].
In the present case, the diagnosis of M. marinum asso-
ciated disease was delayed, mostly due to the tenosyno-
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Tenosynovitis and Sporotrichoid Disease Due to M. Marinum on a Patient under Anti-TNFα Therapy 297
Figure 3. (a) and (b): Sporotr ichoid nodular skin lesions on
the right hand and arm.
vitis being attributed to the patient’s underlying disease.
Even though clinically suggestive, the initial papulono-
dular lesions were not integrated in the patient’s expo-
sure history, especially the frequent fish tank manipula-
tion. Lesions are usually singular, but there can occur
multiple ascending lesions along paths of presumed lym-
phatic spread resembling the infection by Sporothrix
schenkii (“sporotrichoid disease”), as it occurred in our
patient after incomplete drainage. Deep infections such
as tenosynovitis (the most frequent), osteomyelitis, ar-
thritis and bursitis occur in 20% to 40% of cases and dis-
seminated disease is only reported in immunocompro-
mised patients [12].
Despite the scarce number of cases that are published
in the English literature (less than 10 to our knowledge),
the uncommon presentation of our case exhibits similari-
ties with the described, most frequently reports of M.
marinum infection in patients with rheumatoid arthritis or
inflammatory bowel disease treated with infliximab or
etanercept, along with systemic corticosteroids.
The diagnosis of M. marinum infection can be chal-
lenging. Apart from being a rare agent of cutaneous in-
fection, only in less than half of the reported cases did
the skin biopsy or wound fluids yield a positive smear
(31%) or a positive culture (40%) [10,13-16]. Addition-
ally, misdiagnosis is frequent and in most cases that are
described, the diagnosis usually requires biopsy or sur-
gery [10].
PPD tuberculin skin testing is positive in most cases
[17] because of cross-reaction with M. tuberculosis. In
the present case, the positivity of both PPD tuberculin
skin test and IGRA assay were most likely due to the M.
marinum infection yet to be diagnosed, erroneously in-
terpreted as latent M. tuberculosis infection.
In all cases that are published in the literature, the mi-
crobiologic and cultural tests remain persistently nega-
tive, even if worsening of the lesions or new ones occur,
after antibiotic treatment is started.
No controlled studies have been conducted to evaluate
optimal treatment regimens for M. marinum infection.
Patients with uncomplicated, localized skin infections
can usually be treated successfully with antibiotic mono-
therapy. Combinations of two or more antibiotics are
used for more serious infections and typically contain
combinations of clarithromycin and minocycline-doxy-
cycline or rifampin-ethambutol and co-trimoxazole for a
minimum of 3 to 6 months. Antibiotic resistance in M.
marinum is relatively rare in strains isolated from nature,
but most isolates are intrinsically resistant to isoniazid
and pyrazinamide and produce β-lactamase. Resistance
to doxycycline and rifampin has been described [12].
The clinical response is generally slow regardless of
the drug(s) utilized, so extended periods of treatment are
required. The treatment duration referred in some of the
studies published is very long: 3 to 6 months of therapy
for localized disease and 12 months for disseminated
disease [12], a mean duration of 7.2 (range, 0 - 29)
months [10]; in one study, the treatment duration ranged
from 4 to 38 (mean, 14.9) weeks [13]; and in a French
study, the treatment duration ranged from 1 to 25 (me-
dian, 3.5) months [9].
Apart from its almost always important contribute to
diagnosis, surgery is frequently necessary to successful
treatment of deep infections in immunosuppressed pa-
tients [18]. Some authors also describe the more pro-
longed persistence of skin lesions in immunocompro-
mised patients than in normal hosts, with surgical treat-
ment often being required in the former group [1].
The initial misdiagnosis of the M. marinum osteoar-
ticular infection can lead to intralesional injection of cor-
ticosteroid that favors local dissemination. In some stud-
ies, steroids injections into the lesion, persistent drainage
sinus tract after several months of antimicrobial therapy,
and persistent pain were associated with an unfavorable
clinical course and delayed healing of the wound, which
necessitated surgical debridement [19].
The extension of the cutaneous infection to deeper
structures in this case was probably related to the initial
intensification with immunomodulating biologic therapy,
as well as the initial non-aggressive surgical approach,
which probably didn’t eliminate the infectious suppura-
tive foci, essential to a favorable response to medical
treatment. Despite the severity of the clinical presenta-
tion in our case, similarly to the cases published, an in-
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Tenosynovitis and Sporotrichoid Disease Due to M. Marinum on a Patient under Anti-TNFα Therapy
tensive surgical approach along with extended antibiotic
treatment led to an excellent functional outcome [9,10,
However, the optimal treatment of the persistent rheu-
matologic disease in these patients is yet to be defined.
While the discontinuance of the immunomodulating bio-
logic agents is essential to achievement of cure and full
recovery, some authors report safe re-exposition to anti-
TNFα therapy after successful bacterial elimination [20].
4. Conclusion
The deep muscular and articular involvement by M. ma-
rinum related to immunomodulating biologic therapy de-
scribed in this case is rarely reported. Since the patients
who require anti-TNFα therapies are usually at higher
risk of developing infections given their underlying dis-
ease and prior or concurrent treatment with other immu-
nosuppressive drugs, a high index of suspicion for the
infectious complication is needed. A proper exposure
history, particularly in less common clinical presenta-
tions, is very important. The diagnosis of M. marinum
infection is difficult, because the presentation is often
insidious and non-specific, especially when water or fish
exposure is not established. The diagnosis relied on iso-
lation of acid-fast bacilli subsequently identified as M.
marinum. In this case, M. marinum infection presented as
two papulonodular lesions on a hand and progressed to
severe tenosynovitis after anti-TNFα therapy and took a
“sporotrichoidform” after incomplete drainage. The treat-
ment required aggressive surgery, along with extended
anti-infectious therapy and discontinuance of the immu-
nomodulating drugs.
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