Tenosynovitis and Sporotrichoid Disease Due to <i>M. marinum</i> on a Patient under Anti-TNF<i>α</i> Therapy

doi:10.4236/aid.2013.34045

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Advances in Infectious Diseases, 2013, 3, 295-299

Published Online December 2013 (http://www.scirp.org/journal/aid)

http://dx.doi.org/10.4236/aid.2013.34045

Open Access AID

295

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.

Email: †[email protected]

Received September 26th, 2013; revised October 26th, 2013; accepted November 4th, 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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

elsewhere.

#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

296

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)

(e) (f)

(g)

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

(a)

(b)

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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298

tensive surgical approach along with extended antibiotic

treatment led to an excellent functional outcome [9,10,

13].

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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