Clinical, immunological, and genetic features in 938 patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a systematic review.

Background: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare inborn immune error characterized by a triad of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HP), and adrenal insufficiency (ADI).Methods: Literature search was conducted in PubMed, Web of Science, and Scopus databases using related keywords, and included studies were systematically evaluated.Results: We reviewed 938 APECED patients and the classic triad of APECED was detected in 57.3% (460 of 803) of patients. CMC (82.5%) was reported as the earliest, HP (84.2%) as the most prevalent, and ADI (72.2%) as the latest presentation within the classic triad. A broad spectrum of non-triad involvements has also been reported; mainly included ectodermal dystrophy (64.5%), infections (58.7%), gastrointestinal disorders (52.0%), gonadal failure (42.0%), neurologic involvements (36.4%), and ocular manifestations (34.3%). A significant positive correlation was detected between certain tissue-specific autoantibodies and particular manifestations including ADI and HP. Neutralizing autoantibodies were detected in at least 60.0% of patients. Nonsense and/or frameshift insertion-deletion mutations were detected in 73.8% of patients with CMC, 70.9% of patients with HP, and 74.6% of patients with primary ADI.Conclusion: Besides penetrance diversity, our review revealed a diverse affected ethnicity (mainly from Italy followed by Finland and Ireland). APECED can initially present in adolescence as 5.2% of the patients were older than 18 years at the disease onset. According to the variety of clinical conditions, which in the majority of patients appear gradually over time, clinical management deserves a separate analysis.

Autoimmunity in common variable immunodeficiency: a systematic review and meta-analysis.

Objectives: Common variable immunodeficiency (CVID) is the most common symptomatic inborn error of immunity characterized by variable clinical manifestations. Methods: Web of Science, Scopus, and PubMed databases were searched systemically to find eligible studies from the earliest available date to February 2020 with standard keywords. Pooled estimates of the autoimmunity prevalence and the corresponding 95% confidence intervals (CI) were calculated using random-effects models. Results: The overall prevalence of autoimmunity was 29.8% (95% CI: 26.4-33.3; I2 = 82.8%). The prevalences of hematologic autoimmune diseases, autoimmune gastrointestinal disorders, autoimmune rheumatologic disorders, autoimmune skin disorders, and autoimmune endocrinopathy in CVID patients were 18.9%, 11.5%, 6.4%, 5.9%), and 2.5%, respectively. There were significantly higher lymphocyte, CD3 + T cell, and CD4 + T cell count among CVID patients without autoimmunity (p< 0.05). Furthermore, failure to thrive, organomegaly, enteropathy, and meningitis was significantly higher in CVID patients with autoimmunity(p< 0.05). Conclusions: Many CVID patients could present with autoimmunity as part of the disease or even as the first or only clinical manifestation of the disease. Care providers may need to pay particular attention to the possible association of these two disorders since the co-occurrence of CVID and autoimmunity could be a misleading clue.

Infectious Complications Reporting in Common Variable Immunodeficiency: A Systematic Review and Meta-analysis.

OBJECTIVES: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by hypogammaglobulinemia and increased susceptibility to recurrent infections. METHODS: We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2018 with standard keywords. Pooled estimates of the infection prevalence and the corresponding 95% confidence intervals were calculated using random-effects models. RESULTS: We found that pneumonia (67.7%) was the most prevalent infection followed by upper respiratory tract (59.0%) and gastrointestinal infections (36.3%). Furthermore, bacterial complications (41.7%) were higher in CVID patients compared to viral (25.4%), parasitic (18.8%), or fungal (3.4%) infections. Patients with longer age at diagnosis presented with fewer disease comorbidities. There was an inverse correlation between T lymphocyte count and viral infections. Moreover, we found that immunoglobulin M (IgM) serum level was inversely correlated with hepatitis C and gastrointestinal infections, and IgG serum level was inversely correlated with infectious arthritis. Higher numbers of CD4 and CD8 T cells were associated with the lower frequencies of otitis media. CVID patients with infections had significantly lower percentages of CD3 T cells. In contrast, higher percentages of CD19 lymphocytes were found in CVID patients who had a history of infections. CONCLUSIONS: Our findings demonstrated that in addition to hypogammaglobulinemia, patients with CVID have an imbalance in the frequency of T lymphocytes, which is in parallel with the higher frequency of infectious complications.

Combination antifungal therapy without craniotomy in an immunocompromised patient with rhino-orbito-cerebral mucormycosis: A case report.

BACKGROUND: Mucormycosis is an uncommon fungal infection caused by the members of the order Mucorales. In susceptible patients, mucormycosis can infect any tissue or organ, and without suitable treatment (i.e., debridement and antifungal therapy), this infection can be fatal. Our patient was a woman with lymphoma and cerebral mucormycosis who was treated with antifungals and without any neurosurgical debridement. CASE PRESENTATION: Herein, we present the case of a 35-year-old woman with diagnosis of B-cell lymphoma and rhino-orbito-cerebral mucormycosis (ROCM). She was a candidate for enucleation of the left eye, orbital decompression, and sinocerebral debridement. Nevertheless, the patient refused eye enucleation and craniotomy. Finally, she was treated with a combination of antifungals and sinus debridement without eye enucleation and craniotomy. CONCLUSION: debridement, along with a combination of liposomal amphotericin B (LAMB) and posaconazole, may be a suitable therapeutic option for patients with ROCM, who are not eligible candidates for extensive surgery or craniotomy.