Subcutaneous Sweet syndrome associated with disseminated nontuberculous mycobacterial infection leading to the diagnosis of adult-onset immunodeficiency
Authors: Hsiao-Han Wang, Yu-Chen Huang, Wei-Yu Chen, Ying-Yi Chiang
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: A 51-year-old woman without notable medical history presented with multiple 1.5- to 2-cm tender, erythematous, and swollen nodules over the legs, ankles, and soles (Fig 1) for 2 weeks. Fever up to 39°C with chills was also noted. The remainder of the physical examination revealed unremarkable findings. Laboratory tests showed leukocytosis with neutrophilia (white blood cell count 18,280/uL with segments:75.1%), increased C-reactive protein (14 mg/dL), and elevated erythrocyte sedimentation rate (60 mm/h). Histopathological examination of the skin lesion showed neutrophilic lobular panniculitis without vasculitis or any micro-organisms seen in special stains (Fig 1). Blood chemistry, urinalysis, antistreptolysin O antibody, hepatitis B virus surface antigen, antihepatitis C virus antibody, antinuclear antibody, cryoglobulins, antineutrophilic cytoplasmic antibodies, and blood along with tissue cultures produced negative or normal results. Chest x-ray and chest computed tomography showed mediastinal and right hilar lymphadenopathy. Sputum cytology and culture were negative for malignant cells or infection. The patient declined computed tomography–guided lymph node biopsy for investigation of inflammatory, infectious, or neoplastic diseases. The skin lesions gradually improved after cefazolin and diclofenac use. Because of uncertain origin of the lymphadenopathy and possible occult infection, corticosteroid was not further administered. However, multiple tender erythematous nodules over bilateral forearms occurred 1 month later and the histologic examination revealed the same finding as the previous skin biopsy specimen. Tissue culture was still negative for bacteria, fungi, and acid-fast bacilli. There was no detection of tuberculous or nontuberculous mycobacterial (NTM) in the skin tissue by polymerase chain reaction amplification. In addition, progressively enlarged and tender lymph nodes over bilateral neck (Fig 2) and intermittent periods of fever were noticed. Follow-up blood tests showed persistent leukocytosis, anemia, and elevated C-reactive protein and erythrocyte sedimentation rate levels with unremarkable findings in autoimmune profiles, tumor markers, and viral serology. Bone-marrow biopsy specimen revealed reactive hyperplasia. Computed tomography scan showed disseminated cervical, bilateral hilar, and intraabdominal lymphadenopathy (Fig 2). Histologic examination of one of the cervical nodes showed the presence of few acid fast–positive bacilli. The culture of the biopsied lymph node yielded Mycobacterium abscessus. Sputum culture also showed the same species. The aforementioned findings were consistent with the diagnosis of subcutaneous Sweet syndrome associated with disseminated NTM infection. Further immunologic surveys including HIV, absolute T-lymphocyte counts, and autoimmune indicators revealed normal findings. However, high-titer anti–interferon-γ autoantibodies were detected and pointed to the diagnosis of adult-onset immunodeficiency. The patient received amikacin and imipenem for 2 months and continued on prolonged doxycycline and clarithromycin use. Classic Sweet syndrome has been well documented as a reaction to NTM infections.1Choonhakarn C. Chetchotisakd P. Jirarattanapochai K. Mootsikapun P. Sweet's syndrome associated with non-tuberculous mycobacterial infection: a report of five cases.Br J Dermatol. 1998; 139: 107-110Crossref PubMed Scopus (36) Google Scholar However, subcutaneous Sweet syndrome is mostly associated with myeloid disorders,2Chan M.P. Duncan L.M. Nazarian R.M. Subcutaneous Sweet syndrome in the setting of myeloid disorders: a case series and review of the literature.J Am Acad Dermatol. 2013; 68: 1006-1015Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar and some isolated cases with multiple myeloma, breast carcinoma, and Salmonella enteritidis infection.3Guhl G. Garcia-Diez A. Subcutaneous sweet syndrome.Dermatol Clin. 2008; 26 (viii-ix): 541-551Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar We here describe a patient with subcutaneous Sweet syndrome associated with disseminated NTM. Adult-onset immunodeficiency related with anti–interferon-γ autoantibodies has been recently documented predominantly in East Asians.4Chetchotisakd P. Kiertiburanakul S. Mootsikapun P. Assanasen S. Chaiwarith R. Anunnatsiri S. Disseminated nontuberculous mycobacterial infection in patients who are not infected with HIV in Thailand.Clin Infect Dis. 2007; 45: 421-427Crossref PubMed Scopus (93) Google Scholar, 5Browne S.K. Burbelo P.D. Chetchotisakd P. Suputtamongkol Y. Kiertiburanakul S. Shaw P.A. et al.Adult-onset immunodeficiency in Thailand and Taiwan.N Engl J Med. 2012; 367: 725-734Crossref PubMed Scopus (334) Google Scholar Reactive skin diseases with disseminated NTM infection presented as common manifestations.4Chetchotisakd P. Kiertiburanakul S. Mootsikapun P. Assanasen S. Chaiwarith R. Anunnatsiri S. Disseminated nontuberculous mycobacterial infection in patients who are not infected with HIV in Thailand.Clin Infect Dis. 2007; 45: 421-427Crossref PubMed Scopus (93) Google Scholar, 5Browne S.K. Burbelo P.D. Chetchotisakd P. Suputtamongkol Y. Kiertiburanakul S. Shaw P.A. et al.Adult-onset immunodeficiency in Thailand and Taiwan.N Engl J Med. 2012; 367: 725-734Crossref PubMed Scopus (334) Google Scholar However, detailed diagnostic process and histopathological findings were not thoroughly demonstrated, especially with reactive skin lesions as the first clinical manifestation. We herein report a patient with disseminated NTM infection manifested as subcutaneous Sweet syndrome first and further leading to the diagnosis of adult-onset immunodeficiency related to high-titer anti–interferon-γ autoantibodies. Clinicians should be aware that cutaneous symptoms may be the initial manifestations of an undetected infection and an undiagnosed immunodeficiency syndrome.