630 Case Reports Scand J Infect Dis 34

Persistent Ulcers on the Hand of an AquariumOwnerANDREJ TRAMPUZ1, CHRISTIAN GARZONI1, URSULA FLUCKIGER1 andWERNER ZIMMERLI2

From the 1Division of Infectious Diseases, Department of Internal Medicine, University Hospitals, Basel, Switzerland and2University Medical Clinic, Liestal, Switzerland

We present a patient with skin ulcers that did not respond to a 3-week course of treatment with amoxicillin–clavulanic acid.As the patient maintained a � sh aquarium, mycobacterial infection was suspected. Indeed, reassessment of histopathologyrevealed acid-fast bacilli, and mycobacterial cultures at 30 °C grew Mycobacterium marinum. Eventually, surgical recon-struction of the tendons was needed.

W. Zimmerli, MD, University Medical Clinic, Rheinstrasse 26, CH-4410 Liestal, Switzerland. Tel.: »41 61 9252525; Fax:»41 61 925 28 04; E-mail: werner.zimmerli@ksli.ch

INTRODUCTION

Mycobacterium marinum is a well-described cause of cuta-neous infections manifested by cutaneous ulcers, nodules ornodular lymphangitis. The infection usually follows percu-taneous exposure to contaminated fresh- or salt water, or isrelated to injuries with � sh spines. If untreated, mycobacte-rial infections can result in signi� cant morbidity. Wepresent a patient with an unrecognized M. marinum infec-tion that progressed over the course of 6 months, withdestruction of deeper structures of the hand.

CASE REPORT

A previously healthy 72-y-old man was referred to the Division ofInfectious Diseases, University Hospitals, Basel with a 6-monthhistory of 3 painless nodules on the back of his left hand. Thepatient could recall no previous injury and reported no fever, nightsweats or weight loss. Three months previously, a rheumatologisthad suspected a rheumatoid nodule and injected steroids into thelesions. The nodules gradually progressed and ulcerated 1 weekafter the steroid injection. A swab culture from the ulcer grewnumerous colonies of Staphylococcus aureus. Oral amoxicillin–clavulanic acid, 500 mg:125 mg t.i.d., was given for 3 weekswithout any clinical improvement.

The patient presented with 3 ulcers on his left hand, the largestbeing 4 cm in diameter (Fig. 1). The extensor tendons of the 2nd,3rd and 4th digits were partially destroyed. Two additional erythe-matous nodes were present on the distal forearm. Cubital andaxillary lymph nodes were not enlarged, and the remainder of theclinical examination was normal. Blood cell and differentialcounts, as well as CRP value, were normal. X-rays of the handshowed no evidence of bone destruction. Biopsies of the ulcerrevealed non-speci� c neutrophilic in� ammation withoutgranulomas.

Repeated questioning of the patient revealed that he maintaineda tropical � sh aquarium at home. Therefore, we asked for reassess-ment of the tissue histopathology. A few acid-fast bacilli weredetected in the specimen, but no granulomas, epitheloid cells orgiant cells were seen. Treatment with ethambutol 1200 mg daily,rifabutin 300 mg daily and clarithromycin 500 mg t.i.d. for sus-pected M. marinum infection was initiated immediately. After 2weeks of incubation at 30 °C, M. marinum was grown from tissuespecimens using radiolabeled broth medium (BACTEC system).

After 4 months of treatment, the patient developed disablinggeneralized arthralgias, probably due to rifabutin. After discontin-uing rifabutin, arthralgias disappeared within a week. Treatmentwas continued with ethambutol and clarithromycin for the next 2months. Skin lesions healed after 5 months of antimycobacterialtreatment. Seven months after healing of the ulcers, surgical recon-struction of the tendons was performed. At follow-up 12 monthsafter surgery, the patient had recovered fully, with only a littleresidual scarring.

DISCUSSION

M. marinum is a slow-growing, non-tuberculous, pho-tochromogenic mycobacterium. The colonies are whitewhen grown in the dark and turn a brilliant yellow soonafter exposure to light. The organism inhabits fresh- andsalt water and can be found in aquatic organisms world-wide (1). In humans, infection is usually acquired throughcontamination of minor skin abrasions during the cleaningof an aquarium, the handling of � sh or during swimming(2). After a typical incubation period of 2–6 weeks, apainless nodule or pustule develops at the inoculation site,which breaks down to form a crusted ulcer or an abscess(3). Whilst some lesions resolve spontaneously, most persistand progress slowly. M. marinum often spreads alonglymph vessels, leading to nodular or ulcerated satellitelesions. Without treatment, M. marinum may extend tojoints, bone and tendons (4, 5). In an immunocompromisedhost disseminated infections may occur (6, 7).

This case report demonstrates that diagnosis of a M.marinum infection requires a high index of suspicion. Inthis case, the pertinent history was missed, because thepatient was not questioned about possible exposures occur-ring months before the onset of symptoms. The steroidinjection most likely caused additional disease progressionand ulceration of the nodule. In addition, the pathologistand microbiologist should be informed about the suspicionof M. marinum infection so that acid-fast or � uorescentstaining and special cultures can be performed under opti-mal growth conditions. Appropriate culture media for my-

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Scand J Infect Dis 34 Case Reports 631

Fig. 1. Persistent ulcers on the dorsum of the patient’s hand,caused due to infection with M. marinum.

have shown good in vitro activity (12). In retrospectivestudies, the combination of ethambutol and rifampicin (orrifabutin) appears more effective than combinations ofamikacin, minocycline or trimethoprim–sulfamethoxazole(3, 13). For deep infections, a combination ofclarithromycin with ethambutol and:or rifabutin combinedwith surgical treatment is suggested (14). Response to treat-ment is slow and therapy must be continued for severalweeks after cutaneous lesions have disappeared. Thus,treatment is usually continued for 3–6 months. For severeinfections involving persistent and:or deep lesions, surgicaldebridement must be performed in addition.

The differential diagnosis of persistent skin ulcers, notresponding to usual antimicrobial treatment, includes my-cobacteriosis, sporotrichosis, nocardiosis, cat-scratch dis-ease, underlying osteomyelitis and tularemia. Possiblenon-infectious causes include rheumatic diseases, sar-coidosis, skin tumors and foreign body reactions. In addi-tion, melioidosis, yaws, cryptococcosis, histoplasmosis,blastomycosis, coccidiomycosis and leishmaniasis should beconsidered in endemic areas (15).

In conclusion, a properly obtained history with an em-phasis on exposure to tropical � sh or other potentialsources of M. marinum infection is paramount to ensurethe correct diagnosis in patients with persistent ulcers.

REFERENCES

1. Falkinham JO III. Epidemiology of infection by nontubercu-lous mycobacteria. Clin Microbiol Rev 1996; 9: 177–215.

2. Jernigan JA, Farr BM. Incubation period and sources ofexposure for cutaneous Mycobacterium marinum infection:case report and review of the literature. Clin Infect Dis 2000;31: 439–43.

3. Ang P, Rattana-Apiromyakij N, Goh CL. Retrospective studyof Mycobacterium marinum skin infections. Int J Dermatol2000; 39: 343–7.

4. Edelstein H. Mycobacterium marinum skin infections. Reportof 31 cases and review of the literature. Arch Intern Med 1994;154: 1359–64.

5. Harth M, Ralph ED, Faraawi R. Septic arthritis due toMycobacterium marinum. J Rheumatol 1994; 21: 957–60.

6. Parent LJ, Salam MM, Appelbaum PC, Dossett JH. Dissemi-nated Mycobacterium marinum infection and bacteremia in achild with severe combined immunode� ciency. Clin Infect Dis1995; 21: 1325–7.

7. Ekerot L, Jacobsson L, Forsgren A. Mycobacterium marinumwrist arthritis: local and systematic dissemination caused byconcomitant immunosuppressive therapy. Scand J Infect Dis1998; 30: 84–7.

8. Gluckman SJ. Mycobacterium marinum. Clin Dermatol 1995;13: 273–6.

9. Woods GL. Susceptibility testing for mycobacteria. Clin InfectDis 2000; 31: 1209–15.

10. Palenque E. Skin disease and nontuberculous atypical my-cobacteria. Int J Dermatol 2000; 39: 659–66.

11. Ena P, Sechi LA, Saccabusi S, Molicotti P, Lorrai MP, SiddiM, et al. Rapid identi� cation of cutaneous infections by non-tubercular mycobacteria by polymerase chain reaction-restric-tion analysis length polymorphism of the hsp65 gene. Int JDermatol 2001; 40: 495–9.

cobacteria include egg- (Lowenstein–Jensen) or agar-basedsolid media (Middlebrook), as well as broth media forrapid detection.

Using optimal culture techniques for these fastidiousorganisms, which involve the incubation of multiple tissuesamples or discharge � uid at 30–32 °C, organisms may begrown in up to 90% of M. marinum infections, and requiredays to weeks (8). Susceptibility testing should be consid-ered only in patients who do not respond clinically or whocontinue to have positive culture results, as the species isconsistently susceptible to several antimicrobial agents (9).Tissue samples may reveal neutrophilic in� ltration in theacute phase and non-caseous granulomas later in the courseof the disease. Acid-fast bacilli are seen in 10–50% of cases(10). In future, PCR and other molecular techniques maysupersede conventional culture methods for rapid diagnosis(11).

Treatment strategies are not well established because ofthe paucity of cases and scarce clinical experience. Forsuper� cial lesions, antimicrobial treatment without surgerymay be suf� cient. Rifampicin, rifabutin, amikacin, tetracy-clines (e.g. doxycycline, minocycline), sulfamethoxazole,macrolides (e.g. clarithromycin, azithromycin) andquinolones (e.g. cipro� oxacin, levo� oxacin, moxi� oxacin)

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12. Aubry A, Jarlier V, Escolano S, Truffot-Pernot C, Cambau E.Antibiotic susceptibility pattern of Mycobacterium marinum.Antimicrob Agents Chemother 2000; 44: 3133–6.

13. Leuenberger R, Bodmer T. Clinical presentation and therapyof Mycobacterium marinum infection as seen in 12 cases.Dtsch Med Wochenschr 2000; 125: 7–10.

14. Bonnet E, Debat-Zoguereh D, Petit N, Ravaux I, Gallais H.Clarithromycin: a potent agent against infections due to My-cobacterium marinum. Clin Infect Dis 1994; 18: 664–6.

15. Tobin EH, Jih WW. Sporotrichoid lymphocutaneous infec-tions: etiology, diagnosis and therapy. Am Fam Phys 2001; 63:326– 32.

Submitted February 11, 2002; accepted May 21, 2002

DOI: 10.1080:00365540210147688

Zanamivir is an Effective Treatment for In� uenzain Children Undergoing Therapy for AcuteLymphoblastic LeukemiaMIHO MAEDA, YOSHITAKA FUKUNAGA, TAKESHI ASANO, MAKOTO MIGITA,TAKAHIRO UEDA and JUN HAYAKAWAFrom the Department of Pediatrics, Nippon Medical School, Tokyo, Japan

We diagnosed in� uenza infection in 2 children receiving maintenance treatment for acute lymphoblastic leukemia. Bothpatients received zanamivir within 1 d of the onset of fever and their symptoms of in� uenza were rapidly alleviated. Weconclude that inhaled zanamivir seems to be an effective treatment for in� uenza infection in immunocompromised patients.

M. Maeda, MD, Department of Pediatrics, Nippon Medical School, 1-1 -5 Sendagi, Bunkyo -ku, Tokyo 113 -8603, Japan.Tel.: »81 3 3822 2131x6744; Fax: »81 3 5685 1792; E-mail: maeda@nms.ac.jp

INTRODUCTION

In immunocompromised patients, such as those withleukemia, in� uenza can be a serious infection (1). Antiviralprophylaxis is very important but in� uenza vaccines are notnecessarily effective in immunocompromised patients.Amantadine and rimantadine are useful for the preventionand treatment of in� uenza A in immunocompromised pa-tients (2), but infection with in� uenza virus showing resis-tance to these drugs has occurred in some patients (3).Recently, 2 new neuraminidase inhibitors for the treatmentof in� uenza, zanamivir (4, 5) and oseltamivir (6), have beenapproved. Both drugs are highly effective against in� uenzaA and B in subjects without underlying disease. However,there have been no reports on the ef� cacy of neuraminidaseinhibitors for in� uenza infection in immunocompromisedchildren.

CASE REPORTS

Case 1

A 4-y-old boy was diagnosed with acute lymphoblastic leukemia(ALL) in December 1999 and received treatment under theTCCSG L99-15 protocol. From December 2000, maintenance ther-apy was performed with methotrexate (MTX) and 6-mercaptop-urine (6MP). He had a fever (39.3 °C) on the evening of 29January, 2001 and was admitted to our hospital on the followingday. He had no symptoms other than fever. On examination histemperature was 39.9 °C but no abnormalities were revealed apartfrom hyperemia of the pharynx. Hematological tests revealed that

his white blood cell count (WBC) was 6.3½109:l, hemoglobin 138g:l, platelet count 193½109:l and CRP 2.7 mg:dl. A diagnosis ofin� uenza A infection was made using an in� uenza rapid diagnosiskit (Directigen Flu A; Becton-Dickinson, Cockeysville, MD). Atnoon on 30 January, inhalation of zanamivir (10 mg twice daily)was begun, and the fever had resolved by the next morning after 2administrations of the drug. On 2 February, 4 d after beginningzanamivir therapy, the patient again had a fever (38.3–39.0 °C),but this resolved after 1.5 d. He had a cough and slight rhinorrheabut his general condition was good throughout the period from 2d after beginning zanamivir therapy, including the second episodeof fever. His CRP level decreased gradually and became negativeon 13 February. Treatment with zanamivir was continued for atotal of 5 d and no adverse reactions were observed. An in� uenzaserology test performed after 1 month revealed a signi� cant in-crease in antibodies to H3N2. Treatment of leukemia was discon-tinued at the onset of fever but 6MP was restarted on 7 February,4 d after the completion of zanamivir therapy.

Case 2

A 5-y-old girl was diagnosed with ALL in December 1999 and wastreated under the TCCSG L99-15 protocol. From December 2000,maintenance therapy was performed with MTX and 6MP. On thenight of March 20, 2001, she developed a fever (38.5 °C) and asore throat. She was admitted to our hospital on the following day.On examination her temperature was 39.6 °C but no abnormalitieswere revealed, apart from hyperemia of the pharynx. Hematologi-cal tests revealed that her WBC was 6.4½109:l, hemoglobin 137g:l, platelet count 200½109:l and CRP 0.2 mg:dl. A diagnosis ofin� uenza B was made using in� uenza rapid diagnosis kits (Directi-gen Flu A, Becton-Dickinson; and In� uenza OIA, BioStar Inc.,Boulder, CO). Inhalation therapy with zanamivir, 10 mg twice

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