Abstract: We present the case of a 44-year-old woman admitted to our institution with fever, constitutional symptoms, pancytopenia, and splenomegaly. A bone marrow was diagnostic of hairy cell leukemia. The patient was also found to be bacteremic with Mycobacterium abscessus, a highly unusual pathogen in this setting. She responded initially to 4-drug therapy and subsequently was discharge on monotherapy. A review of the case and literature is presented.
*Boston University, Boston; †HIV Clinic, MetroWest Medical Center, Framingham, and ‡University of Massachusetts Medical School, Worcester, MA.
Address correspondence and reprint requests to Jorge Fleisher, MD, MetroWest Medical Center, 115 Lincoln Street, Framingham, MA 01701. E-mail: email@example.com.
A 44-year-old Brazilian woman presented with fever, headache, abdominal pain, vomiting, and weight loss. The illness began approximately 1 week before admission. The initial physical examination was significant for pallor and massive splenomegaly. Severe pancytopenia was present (white blood cell count, 1100/μL; hemoglobin, 6.3 g/dL; and platelet count, 56/μL). A computed tomographic scan of the abdomen revealed massive splenomegaly, and a chest x-ray revealed bilateral interstitial infiltrates with mediastinal lymphadenopathy. The patient received a pack of red blood cells and ceftazidime by vein, but hectic fever continued. A tuberculin test was positive (20 mm). Five days after admission, several blood cultures grew an acid-fast organism. The patient was started on isoniazid, rifampin, pyrazinamide, and ethambutol for presumed tuberculosis. The bone marrow examination was markedly hypercellular and contained a lymphoid infiltrate consistent with hairy cell leukemia (HCL). The blood culture isolate was identified by traditional biochemical testing as Mycobacterium abscessus, and amikacin was added by vein. Initial therapy included granulocyte colony-stimulating factor, interferon α, and splenic radiation. No susceptibility testing was performed for the M. abscessus at that time.
The patient was transferred to a tertiary care hospital for further management. Linezolid, amikacin, moxifloxacin, and clindamycin were initially used for her M. abscessus infection. After 4 weeks of combination therapy, monotherapy with clarithromycin was initiated before discharge and continued for maintenance.
Two months after the discharge, the patient has remained clinically stable without evidence of recurrence, and the abnormalities previously found on the chest x-ray have resolved.
Hairy cell leukemia is an uncommon chronic B-cell lymphoproliferative disorder, representing 2% of all leukemias. Disseminated atypical mycobacterial infection has been associated with HCL, but to our knowledge, this is the first reported case of M. abscessus associated with this disorder. Disseminated mycobacterial infection usually complicates chemotherapy.
Although gram-positive and gram-negative infections are common in patients with neutropenia, patients with HCL have a predilection to develop tuberculosis, atypical mycobacterial infection, and fungal infection, perhaps related to the severe monocytopenia that is characteristic of this disorder. Infections, such as pneumonia and septicemia, are a major cause of morbidity and mortality in patients with HCL.
Mycobacterium abscessus is one of the 8 taxonomic groups of rapidly growing mycobacteria. Clinical disease caused by M. abscessus most often consists of skin or soft tissue infection after trauma. Iatrogenic infections have been documented involving soft tissue abscess secondary to injections with contaminated needles. Other more unusual cases, such as meningitis, have also been reported.1
The first documented case of M. abscessus infection was reported in 1953, when the organism was cultured from synovial fluid and a gluteal abscess in the same patient.2 Thomsen et al,3 in Denmark, were able to collect data regarding the incidence of nontuberculous mycobateria in Scandinavia. After Mycobacterium avium-intracellulare, M. abscessus was the most commonly encountered organism, and the most common presentation was pulmonary infection. Of interest, the authors found a higher predominance of this infection in young individuals with cystic fibrosis. This in contrast with the publication from Sungkanuparph et al4 in Thailand, where the most frequent source of infection was from lymph nodes and skin-related infections. Similar results were obtained from an Australian survey.5 Sungkanuparph et al found a relationship of M. abscessus in patients who presented with lymphadenitis and Sweet syndrome.
There are not many reports, to our knowledge, about M. abscessus bacteremia. Landau et al6 reported 2 cases of immunosuppressed patients, one with adenocarcinoma of the cecum and the other with chronic granulomatous leukemia.
There are reports of atypical mycobacterial infections associated with HCL, specifically, M. avium-intracellulare complex, Mycobacterium kansasii, M. intracellulare, Mycobacterium malmoense, Mycobacterium szulgai, and Mycobacterium chelonae, mainly secondary to neutropenia and immunosuppression caused by chemotherapy. Bennett et al7 published their 10-year experience with atypical mycobacterial infection in patients with HCL. In their review, only one patient presented with mycobacterial bacteremia. The patient grew M. chelonae from blood sample as well as lung biopsy.
Of interest, our patient developed rash on day 11, the skin biopsy showed a vasculitic rash with inflammatory infiltrate containing predominantly mononuclear inflammatory cells, with admixed eosinophils and rare neutrophils consistent with a generalized cutaneous hypersensitivity reaction to a systemic antigen. It has been well described that patients with disseminated M. abscessus can develop a variety of cutaneous manifestations ranging from generalized pustulosis, erythema nodosum, or a nonspecific erythematous rash that usually involves the extremities. Most of the times, special stains of the rash may reveal the causative agent, and culture can also grow the specific mycobacteria.
Mycobacterium abscessus is resistant to all antituberculosis drugs. The best therapy for infection caused by M. abscessus is a controversial topic. On the basis of in vitro susceptibility studies, the preferred parenteral antibiotics have been amikacin and cefoxitin, whereas orally, mycobacteria respond to clarithromycin, azithromycin, quinolones, telithromycin, and linezolid.8-11 Additional potentially useful agents are imipenem and clofazimine. Monotherapy with clarithromycin has been successfully used, although resistance to clarithromycin among isolates of M. abscessus from patients with disseminated disease or chronic lung disease has been observed. There are some reports about synergistic effects of combination therapy. Clarithromycin-amikacin-ethambutol combination has been used extensively because of its synergistic activity as well as bactericidal effect.
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