A Young Boy With Hemophagocytic Lymphohistiocytosis Presenting With Vaccine-Related Granulomatous Dermatitis: A Case Report and Literature Review

Abstract

Cutaneous eruptions associated with hemophagocytic lymphohistiocytosis (HLH) have been reported in 6%-63% of patients. Clinical findings of these skin lesions vary widely and include maculopapular rashes, ulcers, and violaceous nodules. Corresponding histologic findings are also variable and are considered nonspecific. We report the case of a 4-year-old boy who initially developed a widespread popular-pustular rash 2 weeks after his 12month measles, mumps, and rubella vaccinations. These resolved with scarring then recurred following his 24-month vaccinations. Multiple skin biopsies were negative for infectious organisms and showed a granulomatous infiltrate with perforation and necrobiosis. The differential diagnosis included perforating granuloma annulare, infection, or rheumatoid nodules. At the age of 4, he developed fever, hepatosplenomegaly, pancytopenia and other laboratory abnormalities, requiring hospitalization. A number of studies were performed including biopsies of bone marrow and liver. Molecular testing revealed 2 mutations in UNC13D known to be associated with familial HLH. His prior cutaneous lesions were likely caused by immune dysregulation exacerbated by immunizations because of underlying familial HLH. This case illustrates the importance of recognizing an unusual cutaneous manifestation of a rare disease to arrive at an earlier diagnosis in a pediatric patient. Although cutaneous eruptions usually develop concurrently with other systemic symptoms of HLH, preceding unusual skin lesions may be the first indication of this rare disease.

Rubella virus‐associated necrotizing granulomatous inflammation with extensive eyelid, ocular, and orbital involvement

“…However, rubella PCR or immunohistochemistry were not reported. 16 UNC13D-associated disease largely appears to be a recessive condition; thus, the single variant in our patient, even if pathogenic, would not be expected to lead to symptoms. However, the literature does suggest that certain heterozygous variants in UNC13D could potentially have an association with an increased risk for immune dysregulation, [17][18][19] thus the variant may still be significant.…”

“…Of interest, in one case report, a patient with biallelic mutations of UNC13D developed a widespread papular–pustular eruption following MMR vaccination at the age of 2 years, and skin biopsies showed a necrotizing granulomatous process. However, rubella PCR or immunohistochemistry were not reported 16 . UNC13D‐ associated disease largely appears to be a recessive condition; thus, the single variant in our patient, even if pathogenic, would not be expected to lead to symptoms.…”

Atypical familial hemophagocytic lymphohistiocytosis type 3 in children: A report of cases and literature review

“…Another patient with FHL3 presented with vaccine‐related granulomatous dermatitis in the absence of other symptoms. The infiltration of macrophage into the tissue may potentially induce granuloma formation 29 . It is suggested that a rash may also be the primary symptom of FHL3 onset, and the measles–mumps–rubella vaccine should be avoided in cases of cytotoxic dysfunction 30 …”

“…The infiltration of macrophage into the tissue may potentially induce granuloma formation. 29 It is suggested that a rash may also be the primary symptom of FHL3 onset, and the measles-mumps-rubella vaccine should be avoided in cases of cytotoxic dysfunction. 30 The diagnosis of patients with FHL3 is complex.…”

Epstein–Barr Virus‐Positive Hemophagocytic Lymphohistiocytosis Following COVID‐19 Vaccination in a Pediatric Patient

“…HLH can develop with many different immune triggers, including infection and vaccination. 4,5 Reports show HLH in adults can be associated with multiple vaccines, including COVID-19 vaccination. 5 While HLH associated with vaccination is not new, we have yet to understand HLH associated with mRNA-based vaccines in pediatric patients.…”