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Disseminated Mycobacterium avium-intracellulare Complex Infection

      To the Editor:
      Disseminated Mycobacterium avium-intracellulare complex disease primarily occurs in severely immunocompromised patients, such as those with acquired immunodeficiency syndrome, hematologic malignancies, or history of immunosuppressive therapy. Disseminated Mycobacterium avium-intracellulare complex in the immunocompetent host rarely has been reported.
      • Myojo M.
      • Fujiuchi S.
      • Matsumoto H.
      • et al.
      Disseminated Mycobacterium avium complex (DMAC) in an immunocompetent adult.
      • Kahana L.M.
      • Kay J.M.
      • Yakrus M.A.
      • et al.
      Mycobacterium avium complex infection in an immunocompetent young adult related to hot tub exposure.
      • Song J.Y.
      • Park C.W.
      • Kee S.Y.
      • et al.
      Disseminated Mycobacterium avium complex infection in an immunocompetent pregnant woman.
      We describe a case of disseminated Mycobacterium avium-intracellulare complex infection in a previously immunocompetent female. We believe that this extensive involvement of multiple organs with Mycobacterium avium-intracellulare complex in an immunocompetent patient has never been reported.

      Case Summary

      A 23-year-old woman with no medical problems presented with progressively worsening fever, productive cough, weight loss, malaise, chills and dyspnea for 2 weeks. She denied sick contact, exposure to animals, recent travel and history of lymphoma or prior irradiation. On physical examination she had a temperature of 39.7C but otherwise was hemodynamically stable. Chest auscultation revealed diminished breath sounds in the right base. Initial laboratory data showed normal hemogram and chemistry. Chest x-ray showed right lower lobe infiltrate. Patient was started on ceftriaxone and azithromycin for pneumonia. She continued to have fever during the first week of her hospital stay and developed severe pancytopenia.
      Computed tomography scan chest showed a large, right, hilar mass with associated mediastinal adenopathy and bilateral pulmonary nodules and hepatosplenomegaly (Figure).
      Figure thumbnail gr1
      FigureCT scan chest showing large, right hilar mass with mediastinal adenopathy and bilateral pulmonary nodules.
      Blood and sputum cultures remained negative. Workup for human immunodeficiency virus, other viruses, and fungal infections were negative (Table). Fiberoptic bronchoscopy was unremarkable. Bone marrow biopsy was done for pancytopenia which showed hypocelleular marrow and multiple granulomas. Acid-fast bacillus smear, bacterial and fungal cultures were negative.
      TableSummary of Pertinent Laboratory Investigation
      Hemogram
      • Admission: WBC 6.8 × 103; Hb 13 g/dL; Hct 39%; MCV 85fl/cell; platelet count 160 × 103; neutrophils 77%; lymphocytes 16%; monocytes 0.45%
      • Day 7: WBC 0.58 × 103; Hb 7.05 g/dL; Hct; 20.77%; MCV 92.66 fl/cell; platelet count 53 × 103 with neutrophils 76%, lymphocytes 22%, monocytes 0.67%
      • CD 4 cell percentage: 52
      Blood cultures × 2Negative
      Urine culturesNegative
      Sputum cultures, AFB smear and culturesNegative
      Bone marrow culturesNegative
      Cultures AFB, mediastinal lymph nodesPositive for Mycobacterium avium-intracellulare complex
      HIV1 and 2 antibody (enzyme immunoassay)Negative
      Serum CMVantibody IgM, IgGNegative
      Serum EBVantibody IgM, IgGNegative
      Serum Cryptococcal antigenNegative
      Serum Histoplasmosis antigen, urine Histoplasmosis antigen and serum Histoplasmosis antibodiesNegative
      Coccidioidomycosis antibodies IgM, IgGNegative
      Blastomycosis antigenNegative
      HBsAg, anti-HBs, HBcAb, anti HCV Ab, anti HAV IgM antibodyNegative
      AFB=acid fast bacillus; anti-HBs=Hepatitis B surface antibody; CMV=Cytomegalovirus; EBV=Epstein-Barr virus; HAV=Hepatitis A virus; Hb=hemoglobin; HBcAb=Hepatitis B core antibody; HBsAg=Hepatitis B surface antigen; HCV Ab=Hepatitis C antibody; MCV=mean corpuscular volume; WBC=white blood count.
      Her pancytopenia persisted despite multiple transfusions and G-CSF; therefore, she underwent splenectomy and wedge liver biopsy. Pathology showed focal granulomatous inflammation and epithelial granulomas. She finally underwent mediastinoscopic biopsy of lymph nodes that showed necrotizing granulomas and acid-fast bacillus cultures positive for Mycobacterium avium-intracellulare complex.
      Gene mutations in interferon-gamma and interleukin-12 receptors were tested because they have been linked to disseminated Mycobacterium avium-intracellulare complex, but results were negative.
      She was started on azithromycin, ethambutol, and rifampin and discharged on outpatient therapy. She gradually improved and remains symptom free with normalized cell counts.

      Discussion

      Mycobacterium avium-intracellulare complex is the most common non-tuberculosis mycobacterium causing human disease and is primarily a pulmonary pathogen that affects individuals with immunocompromised states. It is found in the environment in soil, natural water, hot tubs, and indoor water systems. The mode of infection is through inhalation or ingestion. In the human immunodeficiency virus–uninfected patient group, disseminated Mycobacterium avium-intracellulare complex infection has been associated with specific mutations in interferon gamma and interleukin 12 synthesis and response pathways.
      • Dorman S.E.
      • Holland S.M.
      Interferon-gamma and interleukin-12 pathway defects and human disease.
      • Casanova J.L.
      • Abel L.
      Genetic dissection of immunity to mycobacteria: the human model.
      Our patient developed pancytopenia after Mycobacterium avium-intracellulare complex involved bone marrow causing secondary bone marrow suppression. Pulmonary lesions, mediastinal lymphadenopathy with necrotizing granulomas, and hepatosplenomegaly were explained by disseminated Mycobacterium avium-intracellulare complex infection.
      Our case elaborates a series of problems associated with Mycobacterium avium-intracellulare complex disease including delay in diagnosis, undefined mode of transmission, and morbidity of the disease.
      Clinicians should consider the diagnosis of Mycobacterium avium-intracellulare complex infection in different clinical conditions. Further studies are needed in patients with disseminated Mycobacterium avium-intracellulare complex disease who are immunocompetent, to look into exact pathogenesis and other genetic mutations involved in the disease process.

      References

        • Myojo M.
        • Fujiuchi S.
        • Matsumoto H.
        • et al.
        Disseminated Mycobacterium avium complex (DMAC) in an immunocompetent adult.
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        • Kahana L.M.
        • Kay J.M.
        • Yakrus M.A.
        • et al.
        Mycobacterium avium complex infection in an immunocompetent young adult related to hot tub exposure.
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        • Song J.Y.
        • Park C.W.
        • Kee S.Y.
        • et al.
        Disseminated Mycobacterium avium complex infection in an immunocompetent pregnant woman.
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        • Holland S.M.
        Interferon-gamma and interleukin-12 pathway defects and human disease.
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        • Abel L.
        Genetic dissection of immunity to mycobacteria: the human model.
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