Cutaneous Mycobacterium chelonae in a liver transplant patient

Cutaneous Mycobacterium chelonae in a liver transplant patient

Cutaneous Mycobacterium chelonae in a liver transplant patient David L. Nathan, MD, Sareeta Singh, MD, Thelda M. Kestenbaum, MD, and J. Michael Caspar...

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Cutaneous Mycobacterium chelonae in a liver transplant patient David L. Nathan, MD, Sareeta Singh, MD, Thelda M. Kestenbaum, MD, and J. Michael Casparian, MD Kansas City, Kansas A 51-year-old woman with an orthotopic liver transplant on tacrolimus (SKF 506) and prednisone presented with an erythematous ulcerated nodule on the knee. No preceding trauma was noted. A skin biopsy specimen demonstrated beaded gram-positive, acid-fast rods and the skin culture grew Mycobacterium chelonae (formerly M chelonae subsp chelonae). This report describes the first case in a liver transplant patient of cutaneous Mycobacterium chelonae under the current method of designating atypical Mycobacterium species. (J Am Acad Dermatol 2000;43:333-6.)

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ycobacterium chelonae subsp chelonae is now designated Mycobacterium chelonae.1,2 M chelonae is normally a saprophyte found in soil and water.3,4 A review of recent literature shows nontuberculous Mycobacterium (NTM) infections are not uncommon in solid organ transplant patients.5 A case of cutaneous involvement caused by Mycobacterium abscessus (formerly Mycobacterium chelonae subsp abscessus) has recently been reported in a liver transplant patient.5 This is the first report of a cutaneous infection in a liver transplant patient with M chelonae under current nomenclature.

CASE REPORT A 51-year-old woman with an orthotopic liver transplant for hepatitis C virus on tacrolimus (SKF 506) and prednisone presented with a 10-day history of a painful lesion on the left knee that was not associated with any preceding trauma (Fig 1). The patient had received a liver transplant 15 months before this admission, with a course that included recurrent hepatitis C infection, intrahepatic biliary stenosis, and numerous bouts of rejection. In addition, 2 months before admission, she had This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. From the Division of Dermatology, Department of Internal Medicine. University of Kansas Medical Center, Kansas City, Kansas. Reprint requests: J. Michael Casparian, MD, Kansas University Medical Center, Division of Dermatology, 4023 Wescoe, 3901 Rainbow Blvd, Kansas City, KS 66160. E-mail: JCASPARI@ KUMC.EDU. Copyright © 2000 by the American Academy of Dermatology, Inc. 0190-9622/2000/$12.00 + 0 16/4/100963 doi:10.1067/mjd.2000.100963

cytomegalovirus (CMV) viremia, requiring treatment with intravenous ganciclovir. On examination, she had an exquisitely tender 1-cm nodule on the left knee. The lesion had an overlying pustule that had ruptured, leaving an erythematous ulceration. Four satellite papules were present, and an erythematous plaque was noted on the left lower leg. There was no regional lymphadenopathy. Chest x-ray radiographs on admission showed scattered granulomas and a probable plural effusion. A skin biopsy specimen demonstrated a polymorphonuclear cell infiltrate that had beaded gram-positive, acid-fast bacilli (Fig 2). Culture demonstrated M chelonae, which was confirmed by polymerase chain reaction. Sensitivity testing revealed the organism was most susceptible to clarithromycin, tobramycin, and imipenem. At the time she presented with skin lesions, her tacrolimus levels were elevated, necessitating a decrease in her dosage of this medication. Within 48 hours of admission, the patient was transferred to the intensive care unit for biliary sepsis, with cultures growing Escherichia coli, enterococcus, and the yeast Torulopsis glabrata. Mycobacterial infection was only detected from the skin lesions. Despite aggressive therapy with early institution of broad-spectrum antibiotics, the patient died from sepsis, renal insufficiency, and acute respiratory distress syndrome.

DISCUSSION The nomenclature of atypical Mycobacterium species has undergone several changes, making interpretation of the literature difficult. In the past, the organisms currently designated as M chelonae and M abscessus were considered subspecies of M 333

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Fig l. Erythematous ulcerated nodule on left knee with several satellite ulcerated papules.

Fig 2. Acid-fast stain of skin biopsy specimen demonstrating many acid-fast bacilli within polymorphonuclear cell infiltrate.

chelonae. Recently, however, M chelonae and M abscessus have been found to have 35% DNA homology, and are now viewed as distinct species.1 A retrospective review of 100 isolates of Mycobacterium chelonae, involving the skin, soft tissue, and bone, reported disseminated disease to occur in 53%, localized disease in 35%, and catheter infections in 12% of the cases.2 Disseminated disease with M chelonae occurs most commonly in immunosuppressed hosts.2 Skin lesions typically present as multiple subcutaneous erythematous nodules, occasionally with multiple draining fistulas, which are typically painful only when large.2 The lesions frequently have an indolent course, and the interval between their appearance and the diagnosis may be many months.6 Typically, constitutional symptoms are absent, and no history of penetrating trauma is elicited.2,6 Conditions associated with disseminated M chelonae infection include organ transplantation, rheumatoid arthritis, vasculitis, and systemic lupus erythematous.2

In contrast to disseminated disease, localized disease typically occurs in immunocompetent patients and presents as a single site of cellulitis, subcutaneous abscess, or osteomyelitis.2 Localized infection typically follows an accidental penetrating injury or medical procedure.2 M chelonae has been associated with soft contact lens use resulting in keratitis,4 and resulting from dog hairs penetrating into the skin.7 Percutaneous catheter associated M chelonae infections may be localized or associated with bacteremia.2,3 Typically, cure requires appropriate antimicrobial therapy, along with catheter removal.3 In a recent review, 82 cases of NTM infections have been documented in solid organ transplant patients: 58 were in kidney transplant patients, 23 in heart transplant patients, and 1 in a liver transplant patient.5 As indicated in Table I, numerous NTM species can induce cutaneous lesions in solid organ transplant patients.5 Cutaneous lesions in this patient population characteristically begin as red to violaceous subcutaneous nodules that may be painful or only mildly

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symptomatic, and may progress to form abscesses or ulcers.5,6 Constitutional symptoms are typically absent.5,6 In one series of cases involving M chelonae in renal transplant patients, the cutaneous lesions have been reported as occurring most commonly on the legs, just as in the case we are reporting in a liver transplant patient.6 However, because these cases were reported under the old classification scheme, many of these transplant patients may have had infection with M abscessus, because only 1 transplant patient had subspecies identification confirming infection with M chelonae.6 Histopathology may show neutrophilic abscesses, along with granulomatous inflammation.8 Our case demonstrated a polymorphonuclear cell infiltrate, and a gram-stain showed gram-positive filamentous bacilli. The gram-positive staining of organisms may suggest Nocardia, a filamentous bacteria that fragments into bacillary segments.4,9 M chelonae is characteristically acid-fast, although the staining may be weak, and these organisms may even be non–acidfast.4 Because Nocardia can also be acid-fast, culturing can differentiate M chelonae from Nocardia, and may identify M chelonae even when the acid-fast stain is negative.4 Because a negative acid-fast smear does not eliminate Mycobacterium as the cause of a lesion, multiple biopsies and cultures may be needed to establish the diagnosis.4,6 In cases where M chelonae is suspected, specimens should be incubated at a temperature between 28°C and 32°C.6 Under these conditions, M chelonae is a rapid growing nontuberculous Mycobacterium, which may grow in 1 week. If the specimen is incubated at 35°C, identification of the organism may be delayed for weeks, or it may fail to grow.6 Polymerase chain reaction has recently become available to confirm the identification of the organism. Optimal treatment is challenging because M chelonae is resistant to many antimicrobials and has variable susceptibilities to others.2,6 M chelonae is typically resistant to traditional antituberculous agents, with the exception of aminoglycosides.6 Recently, clarithromycin has been recommended for the treatment of M chelonae.2,10 Clarithromycin has the advantage of being an oral agent that is 20 to 50 times more active than erythromycin, which, in the past, has been recommended in combination with an aminoglycoside.2,6 Wallace and colleagues10 followed 11 patients who had disseminated cutaneous disease, 9 of whom were given monotherapy with clarithromycin at doses of 500 or 1000 mg twice a day, and 2 of which had an additional antimicrobial as well. Nine patients completed 4.5 to 9 months of therapy without relapse. Of the remaining 2 patients, 1 died of other causes, and was asymptomatic at the time of his death. Another

Table I. Nontuberculous Mycobacterium species associated with cutaneous lesions in solid organ transplant patients5 M kansasii M haemophilum M scrofulaceum M avium intracellulare

M marinum M fortuitum M chelonae M abscessus

patient was noncompliant, discontinuing therapy after 3 months, and had a rapid recurrence with an isolate of M chelonae resistant to therapy.10 Two additional cases of resistance to clarithromycin monotherapy have been reported, one of which occurred in a heart transplant patient.11,12 Therefore, although clarithromycin is often effective as monotherapy, to avoid the emergence of resistance, at least 1 additional antimicrobial agent is recommended as well.10-12 This second agent should be selected on the basis of susceptibility testing. If the isolate shows resistance to all other oral agents, intravenous aminoglycosides may be considered in combination with clarithromycin. The risk/benefit ratio of adding an aminoglycoside needs to be evaluated, however, because the duration of treatment should last for at least several months, based on the findings of Wallace and coworkers.10 For persistent, nonhealing cutaneous lesions, wide excisional surgery with delayed closure, or skin grafting is another treatment option.13 There is a case of disseminated M chelonae infection that proved fatal, before the use of clarithromycin for this condition.14 It is unclear if therapy using clarithromycin and newer antimicrobials will be able to consistently eradicate disseminated cutaneous disease in severely immuncompromised patients. Although immunosuppression can be reduced or eliminated in renal transplant patients, to facilitate healing, this intervention may not be possible in other solid organ transplant recipients.5 The patient in our report was susceptible to disseminated cutaneous M chelonae as a result of the immunosuppression associated with her liver transplant. She was further immunocompromised as a result of having supratherapeutic tacrolimus levels and recent viremia with CMV. Her rapidly deteriorating course and death, associated with biliary sepsis, precluded any determination of the response of her cutaneous lesions to antimicrobial therapy. In conclusion, M chelonae and M abscessus were formerly considered subspecies of M chelonae, but are now viewed as distinct species. This report represents the first case of cutaneous M chelonae infection presenting in a liver transplant patient. NTM,

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including M chelonae, is not rare in solid organ transplant patients and can be expected to occur more frequently as greater numbers of transplant patients live for longer periods. In an immunosuppressed patient, NTM should be in the differential of a nonhealing nodule, particularly on the leg. To establish the diagnosis, not only appropriate staining, but also culturing should be performed, recognizing the temperature sensitive nature of these organisms. Recently, clarithromycin has become recognized as an effective agent in the treatment of cutaneous M chelonae. However, because resistance to monotherapy may develop, and antimicrobial susceptibility varies among isolates, consideration should be made for adding at least one additional agent as determined by sensitivity testing.

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6.

7. 8.

9. 10.

11. REFERENCES 1. Fitzgerald DA, Smith AG, Lees A,Yee L, Cooper N, Harris SC, et al. Cutaneous infection with Mycobacterium abscessus. Br J Dermatol 1995;132:800-4. 2. Wallace RJ Jr, Brown BA, Onyi GO. Skin, soft tissue, and bone infections due to Mycobacterium chelonae chelonae: importance of prior corticosteroid therapy, frequency of disseminated infections, and resistance to oral antimicrobials other than clarithromycin. J Infect Dis 1992;166:405-12. 3. Raad II, Vartivarian S, Khan A, Bodey GP. Catheter-related infections caused by the Mycobacterium fortuitum complex: 15 cases and review. Rev Infect Dis 1991;13:1120-5. 4. Khooshabeh R, Grange JM,Yates MD, McCartney AC, Casey TA. A case report of Mycobacterium chelonae keratitis and a review of

12.

13.

14.

mycobacterial infections of the eye and orbit. Tuber Lung Dis 1994;75:377-82. Patel R, Roberts GD, Keating MR, Paya CV. Infections due to nontuberculous mycobacteria in kidney, heart, and liver transplant recipients. Clin Infect Dis 1994;19:263-73. Cooper JF, Lichtenstein MJ, Graham BS, Schaffner W. Mycobacterium chelonae: a cause of nodular skin lesions with a proclivity for renal transplant recipients. Am J Med 1989;86: 173-7. McKinsey DS, Dykstra M, Smith DL. The terrier and the tendinitis [letter]. N Engl J Med 1995;332:338. Johnson S, Weir TW. Multiple cutaneous ulcers of the legs: Mycobacterium chelonae infection. Arch Dermatol 1993;129: 1190-3. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 7th ed. New York: JB Lippincott; 1990. p. 386-7. Wallace RJ Jr, Tanner D, Brennan PJ, Brown BA. Clinical trial of clarithromycin for cutaneous (disseminated) infection due to Mycobacterium chelonae. Ann Intern Med 1993;119:482-6. Driscoll MS, Tyring SK. Development of resistance to clarithromycin after treatment of cutaneous Mycobacterium chelonae infection. J Am Acad Dermatol 1997;36:495-6. Tebas P, Sultan F, Wallace RJ Jr, Fraser V. Rapid development of resistance to clarithromycin following monotherapy for disseminated Mycobacterium chelonae infection in a heart transplant patient. Clin Infect Dis 1995;20:443-4. Rappaport W, Dunington G, Norton L, Ladin D, Peterson E, Ballard J. The surgical management of atypical mycobacterial soft-tissue infections. Surgery 1990;108:36-9. Paul J, Baigrie C, Parums DV. Fatal case of disseminated infection with the turtle bacillus Mycobacterium chelonae. J Clin Pathol 1992;45:528-30.