A 6-year-old girl presented with facial erythematous plaques that had gradually spread into her limbs over the course of a year (Figure 1A). The center of some erythematous plaques was ulcerated and scabbed spontaneously. She appeared to be predisposed to respiratory infections since birth. Multiple biopsies of the plaques revealed necrotizing granulomatous inflammation (Figure 1D). No microorganisms were identified on PAS and acid-fast stains, tissue cultures, and PCR assays for fungi and mycobacteria. Dense lymphocyte infiltrate with lymphoid follicle formation in the dermis with adnexal involvement was also found in a biopsy from the left upper arm (Figure 1C). Most lymphocytes were T-cells (CD3+) with mixed CD4+ and CD8+ cells. Some lymphocytes showed mild cytological atypia. Clonal expansion of the T-cell population was detected through T-cell receptor gene rearrangement studies. The patient had neutropenia and lymphopenia of T cells, B cells, and NK cells. Specifically, cell counts of CD3+ T cells, CD4+ T cells, and CD8+ T cells were all lower than normal. Subpopulations of the CD3+/CD8-/IL-4+ lymphocytes and CD3+/CD8-/IFN-gamma+ lymphocytes were higher than normal, and CD3+/CD4+/CD25+/FOXP3+ lymphocytes and CD3+/CD8-/IL-17A + lymphocytes were lower than normal. Serum IgA and IgM levels were significantly lower, and the patient's C3 level was slightly lower than normal (Table 1). No clinically significant nodular metabolic enhancement was observed on PET-CT. The timeline of the patient's care is summarized in Figure 2.
Because mycobacterial infections were not ruled out, a diagnostic therapeutic 8-week course of quadruple antituberculosis therapy was performed but without effect. Repeated metagenomic DNA and RNA mNGS analyses were performed, and rubella virus (RuV, read 7280) was detected. A serology test showed RuV IgM was 1.41 S/CO (positive range:>=1), and the RuV IgG titer was 243.7 IU/mL (positive range:>=10). Therefore, a diagnosis of rubella virus-induced cutaneous granulomatous dermatitis was reached.
Considering RuV-associated granulomas are rare and almost exclusively occur in the context of immune deficiency, and the patient had signs of immunodeficiency, a whole- exome sequencing was performed, and heterozygous mutations in DCLRE1C gene as c.352G>T (p.G118X) and c.328C>G (p.L110V) were detected (Figure 3). It was concluded that hypomorphic heterozygous mutations of DCLRE1C genes led to an atypical SCID in this girl, who developed RuV-induced cutaneous granulomatous dermatitis, likely after inoculation with the rubella virus through vaccination. The patient had been waiting for hematopoietic stem-cell transplantation (HSCT) for the previous 10 months, and no other treatments had been initiated. An increase in the number and size of plaques on her face and limbs had been noted (Figure 1B), and the plaques had remained asymptomatic. The patient was hospitalized for pre-transplant examination and preparation.