Cartilage hair hypoplasia with cutaneous lymphomatoid granulomatosis

Abstract

Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia characterized by short-stature, sparse hair and impaired cellular immunity. We describe a young girl who was diagnosed with CHH based on the findings of recurrent infections, short stature with metaphyseal chondrodysplasia, and a confirmed bi-allelic RMRP gene mutation. At 13 years, the patient developed an Epstein-Barr virus (EBV)-driven lymphoproliferative disorder involving the lung, which responded partially to chemotherapy. Simultaneously, she developed multiple indurated plaques involving her face, which had histological findings of granulomatous inflammation and EBV-associated low-grade lymphomatoid granulomatosis. The patient received a matched unrelated peripheral blood stem cell transplant at 15 years of age, and her immunological parameters and skin lesions improved. Lymphomatoid forms of granulomatosis and cutaneous EBV-associated malignancies have not been described previously in CHH. This case highlights the possibility of EBV-associated cutaneous malignancy in CHH.

A 30-Year Prospective Follow-Up Study Reveals Risk Factors for Early Death in Cartilage-Hair Hypoplasia

“…It also emphasizes the need for an aggressive diagnostic approach in symptomatic patients, illustrated by the early detection of lymphoma by gastroscopy performed for vague abdominal pain. Lymphoma development has been reported in CHH children as young as six years (25), as well as in several older children (9, 26, 27). We therefore recommend that screening for lymphoma should begin at 5 years of age.…”

“…Many patients with no symptoms of immunodeficiency developed malignancy during follow-up, suggesting that the pathogenesis of lymphoma in CHH is multifactorial and that the severity of immunodeficiency correlates poorly with the risk of lymphoma. Lymphoproliferative disorders in patients with CHH can be Epstein-Barr virus-driven in some (27, 28), but not all cases (29). Therefore, not only impaired viral suppression, but other mechanisms, such as chromosomal instability, may play a role (30, 31).…”

Immunodeficiency in cartilage‐hair hypoplasia: Pathogenesis, clinical course and management

“…The mechanisms behind autoimmunity in CHH remain obscure. Although the protein microarray demonstrates broad IgG autoantibody multireactivity in serum samples of CHH patients compared to healthy controls, no clinical correlates have been established 52 . However, these findings suggest that B‐cell dysregulation may contribute to the autoimmune manifestations of CHH.…”

Long Non-coding RNA RMRP in the Pathogenesis of Human Disorders

“…Although immunodeficiency is a possible underlying mechanism of malignancy in these patients, many CHH cases with no history of immunodeficiency has developed neoplastic conditions such as lymphoma, implying a multifactorial basis for development of malignancy in CHH (Vakkilainen et al, 2019b). Epstein-Barr virus infection can explain some cases of lymphoproliferative diseases in CHH (Taskinen et al, 2013;Sathishkumar et al, 2018). Yet, not all lymphoproliferative disorders are related with this virus (Nguyen et al, 1718).…”