MIAMI -- Three newly identified syndromes on the clinical research agenda at the National Institutes of Health should be on dermatologists' radar screens, said Dr. Heidi H. Kong.
One of those important "new" syndromes is combined immunodeficiency syndrome associated with mutations in the dedicator of cytokinesis 8 protein (DOCK8). Cutaneous infections and aggressive skin cancers are hallmarks of the syndrome, and both require careful monitoring to help patients control the manifestations of this novel variant of combined immunodeficiency, said Dr. Kong at the annual meeting of the American Academy of Dermatology.
The NIH research described 11 patients (from eight families) who had recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE that are common in some variants of combined immunodeficiency (N. Engl. J. Med. 2010;361:2046-55).
Longitudinal data showed that among the cutaneous manifestations of the disease were recurrent Staphylococcus aureus skin infections with otitis externa, recurrent and severe herpes simplex virus, herpes zoster infections, severe molluscum contagiosum, and human papillomavirus infections. Other findings included severe atopic dermatitis--sometimes including rashes present since birth--with anaphylaxis; extremely aggressive squamous cell carcinomas; and in one patient, T-cell lymphoma/leukemia. This severe cutaneous phenotype of combined immunodeficiency was linked with the DOCK8 mutations.
"Unfortunately, I don't have a lot of treatment recommendations to give for this," said Dr. Kong, a dermatologist and an assistant clinical investigator at the NIH's Center for Cancer Research. "The most important thing we can do for these patients is to monitor for their cutaneous infections and to tend to their skin cancers."
The NIH is currently considering bone marrow transplantation for treating this inherited immunodeficiency, she said.
Other new syndromes that Dr. Kong described were:
Dominant Monocytopenia-Mycobacterial Infection
NIH investigators recently identified and described a subset of patients with nontuberculosis mycobacterial infections who also have monocytopenia, she said.
Dominant monocytopenia-mycobacterial infections are a distinct clinical syndrome involving increased susceptibility to mycobacterial, viral, and fungal infections, as well as malignancy. This can be transmitted in an autosomal dominant pattern, and also occurs sporadically (Blood 2010;115:1519-29).
In 18 patients studied, common infections included HPV and histoplasmosis. Ten patients developed one or more malignancies, including nine myelodysplasia/leukemia, one vulvar carcinoma and metastatic melanoma, one cervical carcinoma, one Bowen's disease of the vulva, and one multiple Epstein-Barr virus leiomyosarcoma.
Patients also commonly develop multiple inflammatory nodules, which usually resolve spontaneously, said Dr. Kong.
Deficiency to the Interleukin-1 Receptor Antagonist
DIRA is a recently discovered subset of the autoinflammatory syndrome that is characterized by a constellation of serious and potentially fatal symptoms, including bone tissue swelling and bone pain and deformity. Inflammation of the periosteum and a rash involving small pustules or extensive pustulosis covering most of a patient's body also occur.
Symptoms typically begin between birth and 2 weeks of age.
Anakinra, a synthetic form of human IL-1Ra, is an extremely effective and well-tolerated treatment for DIRA, Dr. Kong said. Treatment can result in dramatic improvement in the skin within weeks; however, discontinuation leads to relapse within days. Remember this if you are called on to evaluate a newborn with this syndrome, she advised.
Disclosures: Dr. Kong said that she has no relevant conflicts of interest in regard to her presentation.