Disseminated nontuberculous mycobacterial infection with concurrent cutaneous Rosai–Dorfman disease

Disseminated nontuberculous mycobacterial (NTM) infection is a major opportunistic infectious disease that poses a threat to patients with various conditions, including patients with positive HIV results and patients with negative HIV results who carry anti-interferon-γ (anti-IFN-γ) autoantibodies. Among patients with negative HIV results, the most common organs involved in disseminated NTM infection include the lymph nodes, skin and soft tissue, and lungs. Herein, we present a patient who had disseminated NTM infection with concurrent cutaneous Rosai-Dorfman disease (RDD). A 55-year-old male with no underlying diseases was diagnosed in September 2022 with disseminated NTM infection involving the lungs, cervical lymph nodes, and bones. Culture from a computed tomography-guided biopsy of the right iliac bone yielded Mycobacterium kansasii; culture from sputum revealed growth of Mycobacterium abscessus and M. kansasii. Anti-IFN-γ autoantibodies were also detected. The patient was treated with anti-mycobacterial agents, including isoniazid, rifampin, ethambutol, and clarithromycin. Sweet syndrome was observed 3 months later and successfully treated with prednisolone. However, new lesions appeared on neck and chest 6 months later and newly found cervical lymphadenopathies were also observed. He was then referred to our department for further evaluation. Physical examination revealed multiple nontender and enlarged cervical lymph nodes. Multiple erythematous, infiltrative papulonodules and plaques with pustules, erosions, and greasy crusts were distributed along the chin, neck, and chest [Figure 1a and b]. Skin biopsy and culture were performed on an anterior chest lesion. The pathologic report indicated mixed cell infiltration composed of lymphocytes, plasma cells, and neutrophils in the dermis, accompanied by emperipolesis. Special stains, including periodic acid–Schiff and acid-fast stains were negative. An immunohistochemical study indicated the presence of histiocytes and macrophages positive for cyclin D1, S100, and CD68, and negative for CD1a [Supplementary Figure 1]. RDD was strongly suspected, and the patient began treatment with dapsone (100 mg/day) and colchicine (0.5 mg twice daily).Figure 1: (a) Multiple erythematous infiltrative papulonodules and plaques are distributed along the chin, neck, and upper chest with cervical lymphadenopathy. (b) Pustules, erosions, and greasy crusts distributed are over the cutaneous lesions. (c) and (d) Previous lesions regressed with less infiltration and less pustules formation after treatment with dapsone and colchicine for 3 months.Supplementary Figure 1: (a) Dense inflammatory cells infiltrated the dermis (H and E, ×100). (b) Inflammatory cells are composed of numerous plasma cells, neutrophils, and histiocytes (H and E, ×200). (c) Emperipolesis is also observed (H and E, ×400). Immunohistochemical studies reveal histiocytes positive for CD68 (d, ×400), cyclin D1 (e, OM × 400), and S100 (f, ×400).However, mycobacterial culture of biopsied skin tissue revealed growth of M. kansasii. Although the patient continued the anti-mycobacterial treatment because of the disseminated NTM infection diagnosis, his lesions did not improve. Notably, all cutaneous lesions improved partially with less infiltration, and no palpable cervical lymphadenopathies were observed [Figure 1c and d] 3 months following the addition of dapsone and colchicine to the treatment strategy. RDD, also known as sinus histiocytosis with massive lymphadenopathy, is a benign histiocytic proliferative disorder, characterized by massive, painless, and often bilateral cervical lymphadenopathy, accompanied by fever, neutrophilia, anemia, and an elevated erythrocyte sedimentation rate.[1] The etiology remains unknown. RDD has been postulated to represent a disorder of cell-mediated immunity due to cytokine dysregulation in response to infective agents, such as Epstein–Barr virus, HIV, Brucella, and Klebsiella.[2-4] RDD could also be related to autoimmune diseases and hematological malignancies. However, reports of disseminated NTM infection associated with RDD are rare. Tee and Tan[3] reported a case of cutaneous RDD (CRDD) with concurrent NTM infection, where the patient was successfully treated with oral ciprofloxacin and clarithromycin for 7 months. King et al.[5] reported a case where the patient was previously misdiagnosed with RDD but responded poorly to treatment. After further examination, disseminated M. kansasii infection presenting with RDD-like histopathological features was confirmed, and that patient’s lesions resolved completely after treatment with anti-mycobacterial agents. Nevertheless, in our case, the patient’s lesions only improved after dapsone treatment, despite persistent treatment with anti-mycobacterial agents. Sampaio et al.[6] and Chan and Chu[7] reported cases diagnosed with CRDD that failed to respond to isotretinoin and prednisolone, respectively. However, both of them exhibited significant improvements after initiating dapsone monotherapy for several months. Dapsone is an antimicrobial and anti-inflammatory agent that can inhibit myeloperoxidase (MPO), thereby causing cell damage during the process of neutrophilic inflammation. Monocytes, tissue macrophages, and histiocytes also contain MPO. The effect of dapsone was supported by the positive reactions of histiocytes and neutrophils to MPO in the immunohistochemical study conducted by Chan and Chu.[7] Clinicians should avoid making a hasty diagnosis of RDD, even in the presence of characteristic emperipolesis, which has also been reported in rhinoscleroma and H syndrome.[8] In addition, whether NTM infection serves as a possible infective etiology for RDD or whether disseminated NTM infection may exhibit atypical presentations with RDD-like histopathological features should be considered. However, currently, there are still very few relevant research studies that explore the possible pathogenesis. Crucially, our findings in this case revealed that anti-mycobacterial agents alone are inadequate for inducing a substantial response, and additional medication specifically targeting RDD, such as dapsone, should also be considered as part of the therapeutic options, particularly in cases involving dense neutrophilic infiltration. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.