Triple infection with Cryptococcus, varicella-zoster virus, and Mycobacterium abscessus in a patient with anti-interferon-gamma autoantibodies: a case report

Abstract

Background: The most common infection in patients positive for anti-interferon-gamma autoantibodies (anti-IFN-γ AAbs) is disseminated nontuberculous mycobacterial (dNTM) infection. Here, we report a rare case of triple infection caused by Cryptococcus, varicella-zoster virus (VZV), and nontuberculous mycobacterium in a patient with anti-IFN-γ AAbs. Case presentation: A 53-year-old Thai man presented with a progressively enlarging right cervical mass with low-grade fever and significant weight loss for 4 months. He also developed a lesion at his left index finger. A biopsy of that lesion showed granulomatous inflammation with yeast-like organisms morphologically consistent with cryptococcosis. Serum cryptococcal antigen was positive. Histopathology of a right cervical lymph node revealed chronic granulomatous lymphadenitis, and the lymph node culture grew Mycobacterium abscessus. One month later, he complained of vision loss in his left eye and subsequently developed a group of painful vesicles at the right popliteal area of S1 dermatome. Lumbar puncture was performed and his cerebrospinal fluid was positive for VZV DNA. His blood test for anti-HIV antibody was negative. Anti-IFN-γ AAbs was positive, but test for anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF AAbs) was negative. He was treated with amphotericin B plus fluconazole for cryptococcosis; a combination of amikacin, imipenem, azithromycin, and levofloxacin for dNTM infection; and, intravenous acyclovir for disseminated VZV infection. After treatment, our patient's fever and cervical lymphadenopathy were subsided, and his vision and visual acuity were both improved. Conclusions: This is the first case of triple infection with cryptococcosis, VZV, and dNTM in a patient who tested positive for anti-IFN-γ AAbs and negative for anti-GM-CSF AAbs. This case will increase awareness and heighten suspicion of these infections in patients with the described presentations and clinical characteristics, and this will accelerate diagnosis and treatment.

Opportunist Coinfections by Nontuberculous Mycobacteria and Fungi in Immunocompromised Patients

“…isolation in patients' samples. The case reports describe infection cases [116][117][118][119][120][121][122][123][124][125][126], but for several prospective and retrospective studies either it is not clear, or both infection and colonization are present [71,120,[127][128][129][130][131][132]. There is evidence that coinfection by fungal and mycobacterial spp.…”

“…In Table 1, several cases of coinfection by MAC and H. capsulatum are presented, whereas other pathogens such as E.coli [152], herpes virus and Pneumocystis jirovecii [153] were isolated. In two case reports of non-HIV patients, in addition to NTM-fungi coinfection either cytomegalovirus (CMV) or varicella zoster virus were involved [119,122]. Triple coinfections with CMV, MAC and Aspergillus, or varicella zoster virus (VZV), M. abscessus and Cryptococcus, were reported in immunosuppressed patients by cancer or autoimmune disease with IFN-γ antibodies production, respectively [122].…”

“…In two case reports of non-HIV patients, in addition to NTM-fungi coinfection either cytomegalovirus (CMV) or varicella zoster virus were involved [119,122]. Triple coinfections with CMV, MAC and Aspergillus, or varicella zoster virus (VZV), M. abscessus and Cryptococcus, were reported in immunosuppressed patients by cancer or autoimmune disease with IFN-γ antibodies production, respectively [122]. The virulence of the NTM and the imbalance of the host immune system certainly played a role in this outcome.…”

“…infections due to residual or nonexistent activity. Therefore, other azole derivatives, namely itraconazole and voriconazole, are used in the therapy of pulmonary aspergillosis [122]. Severe histoplasmosis cases requiring patient hospitalization are treated with liposomal amphotericin B and therapy is usually changed to itraconazole after one to two weeks.…”

“…The analysis of other case reports summarized in Table 1 shows that amphotericin B and/or new triazole derivatives are the drugs of choice to treat concomitant invasive aspergillosis and NTM infection [119]. In the already mentioned case of a 53-year-old man with combined infection of Cryptococcus, M. abscessus, and VZV [122], amphotericin B together with fluconazole was selected to treat cryptococcosis in combination with amikacin, imipenem, azithromycin and levofloxacin for NTM, and intravenous acyclovir for VZV [122]. In another coinfection case by C. glabrata, M. monocense and other bacteria, voriconazole was administered together with cefoperazone, sulbactam and linezolid, an improvement in the patient's conditions being observed after 10-days therapy [125].…”