Here, we describe a patient with SLE and myasthenia gravis who suffered multiple infectious complications including varicella, CMV syndrome/jejunitis and Legionella panniculitis with possible dissemination (myositis and myocarditis). Panniculitis cause by Legionella has not been reported in the literature. Our initial presumptive diagnosis of panniculitis was lupus panniculitis or CMV related panniculitis. However, our patient did not improve during the course of treatment for both diseases. The diagnosis of lupus panniculitis should not be assumed in SLE patients, given that immunosuppressive drugs are a predisposing factor for infective panniculitis, and both conditions require different treatment strategies [10]. Infective panniculitis has been described in association with many infectious agents including bacteria (Nocardia spp. and Actinomyces spp.), mycobacteria, fungi and parasites [11]. Anatomical pathology is the key to distinguishing the etiology of panniculitis by the type of white blood cell infiltrates. Lupus panniculitis presents with lymphocytic infiltrates with or without vasculitis. CMV panniculitis must have evidence of viral cytopathic changes with the characteristic owl’s eye inclusion bodies. Our patient had neutrophilic panniculitis that suggested infective panniculitis. Gram staining showed intracellular Gram-negative bacilli that failed to grow on routine culture media, and they were identified as L. pneumophila by molecular methods. It was difficult to distinguish whether the panniculitis resulted from primary inoculation or secondary hematogenous spread of Legionella. Several features, such as prolonged fever despite broad-spectrum beta-lactam antibiotics, myositis and myocarditis, suggested disseminated Legionella infection. Myositis has been reported in one patient with pneumonia [12]. The etiology of myocarditis in our patient remains debatable, and whether it resulted from lupus or Legionella infection. Myocardial biopsy was not performed because of the excessive risk in our case, and therapy for both lupus and Legionella was initiated at the same time. Follow-up echocardiography showed normal cardiac function. Legionella myocarditis has been reported as a complication of Legionnaires’ disease [13, 14]. Only one adult patient developed perimyocarditis due to L. pneumophila in the absence of respiratory involvement, which resulted in multiorgan failure [1]. The atypical multiorgan involvement of Legionella infection in our patient could have resulted from immunosuppression that led to lymphopenia and cell-mediated immunodeficiency. Our patient did not have evidence of pneumonia at any time point before or during hospitalization.
Cutaneous and subcutaneous Legionella infection is rare and mostly occurs in immunosuppressed patients, as described previously [5]. Primary extrapulmonary infection of skin/subcutaneous tissue (cellulitis, multiple subcutaneous abscesses, and tenosynovitis) by L. pneumophila led to disseminated infection (pneumonia and respiratory failure) in an immunocompromised liver transplant recipient [15]. The diagnosis was made from culture of bronchoalveolar lavage fluid and later, Legionella was isolated from the abscesses using special culture media and was confirmed by molecular methods [15]. This highlights the challenging aspect in the diagnosis of Legionella infection, as it is a facultative Gram-negative aerobic bacillus that resides within tissue and alveolar macrophages, and it requires specialized media [16]. Non-culture-based diagnostic methods include urinary antigen tests for L. pneumophila, which is a rapid diagnostic tool; however, these tests are limited to the detection of L. pneumophila serogroup 1, L. micdadei and Legionella longbeachae [17].
The diagnosis of extrapulmonary Legionella infection relies on clinician alertness and a good level of cooperation with the microbiology laboratory, as Legionella species must be grown on special media. In our setting we did not have the selective media, Legionella urinary antigen and antibody to detect Legionella, or direct fluorescent antibody against Legionella. The diagnosis in our patient was made by 16S rRNA gene sequencing method. Initiation of appropriate treatment is critical because delay is associated with increased mortality in Legionella pneumonia [18]. Effective antimicrobial treatment of legionellosis includes antibiotics that achieve therapeutic intracellular concentrations within macrophages, such as the macrolides, fluoroquinolones, and cyclin families [16]. Azithromycin or levofloxacin are commonly used to treat Legionella infection [16, 19]. Optimal treatment duration for cutaneous legionellosis has not been established. Most patients with Legionella pneumonia are successfully treated with a 7-to 14-day course of antibiotics. Disseminated legionellosis requires longer duration of therapy, although the duration is not well defined. Immunocompromised patients with cutaneous legionellosis may require 3 weeks of treatment [5, 16].