Atypical Mycobacterial Lymphadenitis



Atypical Mycobacterial Lymphadenitis


Tariq Muzzafar, MBBS










Scanning electron micrograph demonstrates M. chelonae bacteria. (Courtesy J. Carr, CDC Public Health Image Library, #226.)






Acid-fast (Ziehl-Neelsen) stain of lymph node in an AIDS patient shows abundant M. avium-intracellulare within histiocytes. (Courtesy E. Ewing, Jr., MD, CDC Public Health Image Library, #965.)


TERMINOLOGY


Abbreviations



  • Atypical mycobacteria (AM)


Synonyms



  • Nontuberculous mycobacteria (NTM)


  • Mycobacteria other than tubercle bacilli (MOT)


  • Potentially pathogenic environmental mycobacteria (PPEM)


Definitions



  • Lymphadenitis caused by infection by atypical mycobacteria


ETIOLOGY/PATHOGENESIS


Environmental Exposure



  • Widely distributed in soil; also present in natural and treated water sources


  • No evidence of animal-to-human or human-to-human transmission


  • Human infection suspected to be acquired from environmental sources


Infectious Agents



  • M. avium-intracellulare (MAI) is most common organism implicated in lymphadenitis


  • M. scrofulaceum, M. fortuitum, M. chelonei, M. abscessus, M. kansasii also occur but are less common


  • May cause either asymptomatic infection or symptomatic disease


Pathogenesis



  • Nonspecific immunity



    • Epithelial barrier integrity


    • Gastric pH


    • Interleukin (IL)-8, IL-12, chemokine ligand 5 (CCL5)


    • Natural resistance-associated macrophage protein


    • Macrophages initially phagocytose mycobacteria


  • Specific immunity



    • Develops over weeks following infection


    • Mediated by CD4(+) T lymphocytes


    • Involves IL-2, interferon (IFN)-γ, tumor necrosis factor (TNF)-γ


    • IFN-γ activates neutrophils and macrophages to kill intracellular mycobacteria


  • Host defects predispose to disseminated infection



    • Deficiency of CD4(+) lymphocytes in HIV infection



      • Disseminated AM infection when CD4(+) count < 50/µl


    • Specific mutations resulting in IFN-γ receptor defects and reduced IFN-γ production


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Infection rate in North America: 1-12 per 100,000 persons


    • Disease rates: 0.1-2 per 100,000 persons


    • Prevalence of pulmonary AM infection in USA is increasing


    • MAI is most common AM species causing disease


    • Many other species have been implicated


    • Significant percentage of adults have had prior asymptomatic infection with AM as assessed by skin tests


    • Distinguishing infection from disease needs clinical correlation



      • Diagnostic criteria have been defined to guide treatment


      • Infection defined as isolation of viable organisms from uncontaminated specimen in absence of clinical manifestations


      • Disease defined as additional signs or symptoms that suggest pathogenic process



    • Isolation of a single positive sputum culture does not necessarily represent disease


    • No evidence that AM are associated with reactivation of disease


    • Prevention of infections not possible at present


Site



  • Virtually any body site can be infected by AM


Presentation



  • Pulmonary



    • Most common clinical manifestation


    • Immunocompetent patients



      • Tuberculosis-like pattern involving upper lobes in men with history of smoking or lung disease


      • Nodular bronchiectasis in slender older nonsmoking women with skeletal deformities; presents with cough


      • Hypersensitivity pneumonitis associated with hot tubs and medicinal baths; presents with dyspnea, cough, and fever


      • M. kansasii, M. xenopi, M. malmoense, and MAI implicated in tuberculosis-like pattern


      • MAI implicated in all nodular bronchiectasis and hypersensitivity pneumonitis patterns


      • Isolated pulmonary disease due to MAI occurs typically in immunocompetent adults


    • Immunocompromised (HIV+)



      • AM commonly isolated from respiratory secretions


      • Isolated lung disease uncommon


      • Extrapulmonary or disseminated disease more likely


      • M. kansasii can cause lung disease without dissemination


    • Diagnosis of pulmonary MAI based on clinical, microbiological, and radiographic criteria


  • Lymph nodes



    • Painless swelling of one or more lymph nodes in regional distribution


    • Anterior cervical lymph nodes most commonly affected



      • Submandibular, submaxillary, and preauricular


    • Parotid, postauricular, mediastinal lymph nodes can be involved


    • Peak incidence at 1-5 years of age



      • MAI isolated in 80% of culture-positive cases in children


      • Other species: M. scrofulaceum, M. malmoense, and M. haemophilum


      • Recently identified slow-growing mycobacteria have also been implicated


    • No systemic symptoms


    • Indolent disease


    • Unilateral in 95% of cases


    • Route of infection hypothesized to be lymphatics draining mouth and oropharynx


    • Lymph nodes enlarge and may rapidly soften and rupture


    • Chronic, draining fistulae to skin can result


    • Spontaneous regression can occur


    • Healing usually occurs by fibrosis and calcification


    • Uncommon in adults except AIDS patients in era of highly active antiretroviral therapy (HAART)



      • In past, MAI disease in AIDS patients was disseminated process


      • With advent of HAART, lymphadenitis can occur as part of immune reconstitution syndrome


    • Diagnosis of AM lymphadenitis requires either positive culture or suggestive histopathology after ruling out M. tuberculosis infection


    • Most patients have < 10 mm reaction due to crossreactivity between M. tuberculosis and AM proteins


    • Induration > 10 mm has been reported in nearly 1/3 of children with AM lymphadenitis


  • Skin and soft tissue



    • MAI infection



      • Occurs by direct inoculation (trauma, surgery, or injection)


      • Ulceration, abscess with sinus formation, erythematous plaque with crusted base ensue


      • Lesions are indolent


      • Diagnosis requires high index of suspicion



      • History of exposure to potential source of infection may be helpful


      • Combination of excision (or surgical debridement) and chemotherapy required


    • Buruli ulcer



      • M. ulcerans is causative organism


      • Tropical and subtropical regions: West and Central Africa, Central and South America, and Southeast Asia


      • Infection thought to occur through cut or wound contaminated with water, soil, or vegetation


      • More common in children < 15 years of age


      • Lower limbs involved more than upper limbs


      • Begins as solitary painless subcutaneous nodule or papule


      • Evolves to form ulcer with undermined edges


      • Spontaneous healing in 4-6 months


      • Extensive scar formation


      • Dissemination, including osteomyelitis, can occur, especially in patients < 15 years old


      • Surgical excision with wide margins required


    • M. marinum infection



      • Worldwide distribution


      • Infection occurs through injury by fish fins or bites, cutaneous trauma, exposure to contaminated water


      • Infections limited to skin and confined to single extremity


      • Tender, erythematous or bluish papulonodular lesion (0.5-3 cm) enlarges slowly and suppurates


      • Infection may spread to deeper structures, leading to scarring


      • Infection may extend to regional lymph nodes


    • Rapidly growing atypical mycobacteria (RGM)



      • Survive in harsh aquatic conditions; piped water systems


      • Resistant to sterilizing agents and disinfectants


      • Immunocompetent: Single lesion after penetrating trauma, surgery; M. fortuitum predominant organism


      • Immunocompromised: Multiple/disseminated lesions after penetrating trauma, surgery; M. chelonae or M. abscessus predominant organisms


      • Identification of RGM at species level essential for deciding treatment regimen


  • Musculoskeletal

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Atypical Mycobacterial Lymphadenitis

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