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Mycobacterium Haemophilum: a Challenging Treatment Dilemma in an Immunocompromised Patient

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Mycobacterium Haemophilum: a Challenging Treatment Dilemma in an Immunocompromised Patient CASE LETTER Mycobacterium haemophilum: A Challenging Treatment Dilemma in an Immunocompromised Patient Nicholas A. Ross, MD; Katie L. Osley, MD; Joya Sahu, MD; Margaret Kasner, MD; Bryan Hess, MD haemophilum infections largely are cutaneous and PRACTICE POINTS generally are seen in AIDS patients and bone marrow • Mycobacterium haemophilum is a slow-growing transplant recipientscopy who are iatrogenically immuno- acid-fast bacillus that requires iron-supplemented suppressed.4,5 No species-specific treatment guidelines media and incubation temperatures of 30°C to exist2; however, triple-drug therapy combining a mac- 32°C for culture. Because these requirements for rolide, rifamycin, and a quinolone for a minimum of growth are not standard for acid-fast bacteria cul- 12 notmonths often is recommended. tures, M haemophilum infection may be underrecog- A 64-year-old man with a history of coronary artery nized and underreported. disease, hypertension, hyperlipidemia, and acute myelog- • There are no species-specific treatment guidelines, enous leukemia (AML) underwent allogenic stem cell but extended course of treatment with multiple activeDo transplantation. His posttransplant course was compli- antibacterials typically is recommended. cated by multiple deep vein thromboses, hypogamma- globulinemia, and graft-vs-host disease (GVHD) of the skin and gastrointestinal tract that manifested as chronic diarrhea, which was managed with chronic prednisone. To the Editor: Thirteen months after the transplant, the patient pre- The increase in nontuberculous mycobacteria (NTM) sented to his outpatient oncologist (M.K.) for evaluation infections over the last 3 decades likely is multifaceted, of painless, nonpruritic, erythematous papules and nod- including increased clinical awareness, improved labora- ules that had emerged on the right side of the chest, right tory diagnostics, growing numbersCUTIS of immunocompro - arm, and left leg of approximately 2 weeks’ duration. mised patients, and an aging population.1,2 Historically, On review of systems by oncology, the patient denied the majority of mycobacteria-related diseases are due any fevers, chills, or night sweats but noted chronic to Mycobacterium tuberculosis, Mycobacterium bovis, and loose nonbloody stools without abdominal pain, likely Mycobacterium leprae.3 related to the GVHD. The patient’s medications included Mycobacterium haemophilum is a slow-growing acid- prednisone 20 mg once daily, fluconazole, amitriptyline, fast bacillus (AFB) that differs from other Mycobacterium atovaquone, budesonide, dabigatran, metoprolol, pan- species in that it requires iron-supplemented media and toprazole, rosuvastatin, senna glycoside, spironolactone, incubation temperatures of 30°C to 32°C for culture. tramadol, and valacyclovir. As these requirements for growth are not standard Physical examination revealed multiple singular ery- for AFB cultures, M haemophilum infection may be thematous nodules on the right side of the chest (Figure 1A), 3 underrecognized and underreported. Mycobacterium right arm (Figure 1B), and left leg. There was no regional From Thomas Jefferson University, Philadelphia, Pennsylvania. Drs. Ross, Osley, and Sahu are from the Department of Dermatology & Cutaneous Biology; Dr. Kasner is from the Department of Medical Oncology; and Dr. Hess is from the Department of Medicine, Division of Infectious Diseases. Dr. Sahu also is from the Dermatopathology Center, Jefferson University Hospitals, Philadelphia. The authors report no conflict of interest. Correspondence: Nicholas A. Ross, MD, 833 Chestnut St, Ste 740, Philadelphia, PA 19107. WWW.MDEDGE.COM/DERMATOLOGY VOL. 104 NO. 3 I SEPTEMBER 2019 E7 Copyright Cutis 2019. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. MYCOBACTERIUM HAEMOPHILUM lymphadenopathy. The patient was afebrile and hemo- disseminated mycobacterial infection. The patient was dynamically stable. A biopsy of the arm performed to admitted to our institution approximately 1 week after rule out leukemia cutis revealed a granulomatous der- the outpatient biopsy was performed. He was evaluated matitis with numerous AFB (Figures 2A and 2B), which by infectious diseases (B.H.) and was recommended for were confirmed on Ziehl-Neelsen staining (Figures 2C repeat biopsy with AFB culture and for initiation of intra- and 2D). The presence of AFB raised concern for a venous antibiotics. A copy B FIGURE 1. A, Erythematous nodule on the right chest wall. B, Multiple, discrete, erythematous papules and nodules in a sporotrichoid pattern on the right arm. not Do CUTIS A B FIGURE 2. A and B, Granulomatous dermatitis with numerous acid-fast bacilli was seen on hematoxylin and eosin staining (original mag- nifications ×40 and ×200). C and D, Ziehl- Neelsen staining also confirmed numerous acid-fast bacilli (original magnifications ×20 and ×600). C D E8 I CUTIS® WWW.MDEDGE.COM/DERMATOLOGY Copyright Cutis 2019. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. MYCOBACTERIUM HAEMOPHILUM The patient was evaluated by the dermatology consul- 300 mg once daily. Azithromycin was substituted for tation service on hospital day 1. At the time of consulta- clarithromycin in an attempt to minimize the gastrointes- tion, the lesions were still painless but had enlarged. Two tinal side effects of the antibiotics. The infectious disease new satellite lesions were noted on his other extremities. specialist was concerned that the clarithromycin could Due to the widespread distribution of the lesions, there exacerbate the patient’s chronic GVHD-associated diar- was concern for disseminated disease. The relatively rapid rhea, which posed a challenge to the oncologist, who was onset of new lesions increased concern for infection with attempting to manage the patient’s GVHD and minimize rapid-growing mycobacteria, including Mycobacterium the use of additional prednisone. At the time of this abscessus, Mycobacterium fortuitum, and Mycobacterium change, the patient was doing well clinically and denied chelonae. A detailed history revealed that the patient’s any active skin lesions. wife had a fish tank, which supported the inclusion of Four months later, he developed new left-sided neck Mycobacterium marinum in the differential; however, fur- swelling. Computed tomography revealed nonspecific ther questioning revealed that the patient never came in enhancement involving the skin and superficial subcu- contact with the aquarium water. The initial outpatient taneous tissues in the left anterior neck. He was referred biopsy had not been sent for culture. Following inpatient to otolaryngology given concern for recurrent infection vs biopsy, the patient was initiated on empiric antimyco- leukemia cutis. He underwent excisional biopsy. Pathology bacterials, including imipenem, amikacin, clarithromycin, was negative for malignancy but demonstrated subcuta- and levofloxacin. Computed tomography of the head was neous necrotizing granulomatous inflammation with a negative for cerebral involvement. positive AFB stain. Tissue AFB cultures revealed moder- Acid-fast bacilli blood cultures were drawn per the ate AFB on direct stain, but there was no AFB growth at recommendation from infectious diseases in an attempt 12 weeks. Clarithromycin was restarted in place of azithro- to confirm disseminated disease; however, blood cultures mycin to increase the potency of the antimycobacterial remained negative. Tissue biopsy from the right arm was regimen. Culturescopy from this neck biopsy were negative sent for AFB staining and culture. Many AFB were iden- after 12 weeks of incubation. tified on microscopy, and growth was observed in the In addition to this change in antibiotic coverage, the mycobacterial growth indicator tube after 6 days of incu- patient’s medical oncologist tapered the patient’s immu- bation. The DNA probe was negative for M tuberculosis nosuppression considerably. The patient subsequently complex or Mycobacterium avium complex. completednot 12 months of therapy with clarithromycin, The patient was discharged on hospital day 6 on moxifloxacin, and rifabutin starting from the time of the empiric therapy for rapid-growing mycobacteria while neck biopsy. He remained free of recurrence of mycobac- cultures were pending. The empiric regimen includedDo terial infection for nearly 2 years until he died from an intravenous imipenem 1 g every 6 hours, intravenous unrelated illness. amikacin 1 g once daily, clarithromycin 500 mg every Nontuberculous mycobacteria are an ubiquitous 12 hours, and levofloxacin 750 mg once daily. All solid environmental group.2 Sources include soil and natu- media cultures were negative at the time of discharge. ral water (M avium), fish tanks and swimming pools The biopsy specimen proved difficult to culture on (M marinum), and tap water and occasionally domes- solid media using traditional methods. Three weeks tic animals (Mycobacterium kansasii). Additionally, rap- after the inpatient biopsy, the microbiology labora- idly growing NTM such as M abscessus, M chelonae, tory reported that growth was observed on solid media and M fortuitum have been isolated from soil and natural that was incubated at 30°CCUTIS and supplemented with water supplies.3 iron. These findings were not characteristic of a rapidly Mycobacterium haemophilum is a fastidious organism growing mycobacteria (eg, M fortuitum, M chelonae, with a predilection for skin
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