The Consult Service Staff consists of myself, Dr. John DiGiovanna, and a Nurse Practitioner, Olanda Hathaway, who joined the Branch in 2011. As mentioned above, providing clinical expertise in the assessment and management of the cutaneous disease is a highly valued service to the NIH community which was recognized by the NIH Director's Award in 2007. In addition to seeing patients in Consultation, I am an Associate Investigator on several other protocols initiated by other branches as well as a Principal Investigator on three therapeutic protocols (to be discussed separately). The current non-Dermatology Branch protocols in which I am an Associate Investigator include Natural History of GVHD;Reduced intensity transplants for malignant lymphomas/leukemias;Immune-depleting therapy and reduced intensity transplant using unrelated donors;Allogeneic transplant for DOCK8 Immunodeficiency;Pomalidomide for chronic GVHD;Phase II Montelukast for bronchiolitis obliterans;Sirolimus for Cowdens disease;Erlotinib and bevacizumab for renal cell carcinoma;Natural history of auto-inflammatory diseases;Anakinra for Behcet's disease;Rilonacept for deficiency of the IL-1 antagonist. The chronic graft versus host disease (GVHD) collaborative effort is a major multidisciplinary collaboration with several NCI and non-NCI investigators studying the Natural history of GVHD. Based on my experience with this group, I have published several text chapters and clinical manuscripts on cutaneous GVHD and have been honored to lecture to various groups around the country (Harvard, Tufts, U. of Pennsylvania, the American Academy of Dermatology, regional dermatologic societies, and the World Congress of Dermatology.) Collaborative clinical research is extremely active via the busy consultation service. The newly discovered mutations in pyrin genes in patients with several periodic fever syndromes, and the availability of biologic therapies that have efficacy in the resulting autoinflammatory diseases have introduced a new group of patients to the clinic. We are now systematically characterizing cutaneous manifestations and assessing responses to treatment in patients with PAPA syndrome, Behcets and deficiency of IL-1 receptor antagonist (DIRA). I am Principal Investigator on three protocols: Botulinum toxin for painful leiomyomas (09-C-0072), imatinib mesylate (08-C-0148) for the treatment of sclerotic chronic GVHD, and anakinra for neutrophilic pustular skin disease (13-C-0071). Cutaneous leiomyomas are benign tumors thought to arise from the arrector pili muscle. They may occur as isolated papules, or present as grouped lesions over areas of the body, including the back and extensor surfaces. Individual lesions often range from 5mm to 1cm in size, but can be as large as a few cm in diameter. Cutaneous leiomyomas have been associated with a dominantly inherited cancer-related genodermatosis, hereditary leiomyomatosis and renal cell cancer (HLRCC), which is caused by a mutation in the fumarate hydratase gene. HLRCC is characterized by cutaneous and (in females) uterine leiomyoma formation as well as an increased risk of renal cell cancer. Patients with HLRCC may present with isolated cutaneous lesions, regional areas of involvement, or diffuse leiomyoma formation. Both sporadically occurring and HLRCC-related cutaneous leiomyomas are often painful. In some cases, severe paroxysmal pain may be elicited by stimuli as innocuous as pressure or a change in ambient temperature. Cold-induced pain in cutaneous leiomyomas can be reproduced in a standardized setting with application of an ice cube.1 For patients with symptomatic cutaneous leiomyomas, the pain may be severe enough that patients contemplate suicide. The etiology of the pain symptoms is poorly understood, but the episodic, intense nature of the pain and reported response in some patients to neuroactive agents suggests that manipulation of the nerve conduction pathways may ameliorate pain. The arrector pilorum muscle is under autonomic control. Thus, one would expect that tumors arising from this structure would also be innervated by autonomic nerves that utilize catecholamine neurotransmitters. Immunohistochemical studies have demonstrated an increase in nerve fibers within and surrounding leiomyomas. Nerves within and around leiomyomas stain strongly with acetylcholinesterase, suggesting a role for acetylcholine in leiomyoma innervation. In murine studies, nerve fibers visualized in the arrector pili muscle are immunoreactive to the neuropeptide calcitonin-gene related peptide (CGRP) The pain is hypothesized to be related to pressure on the nerves within the lesions, release of neuropeptides, or muscle contraction mediated via alpha-adrenergic receptors. The current treatments for the paroxysmal pain associated with cutaneous leiomyomas are inadequate. Acetylcholinesterase staining is seen in and around leiomyomas, and CGRP immunoreactivity is present in nerve fibers of arrector pili muscles. Based on the reported effects of BTX-A on acetylcholine and CGRP, we have been studying subjects with symptomatic cutaneous leiomyomas in a pilot study with intralesional administration of BTX-A. The second protocol in which I am principal investigator is the study of imatinib mesylate for the treatment of chronic GVHD (08-C-0148). Imatinib mesylate is a tyrosine kinase inhibitor that was specifically developed to target inhibition of tyrosine phosphorylation of proteins involved in BCR-ABL signal transduction. It additionally has a high degree of specificity and biological activity against both platelet-derived growth factor (PDGF) and transforming growth factor- (TGF-) signaling pathways, cytokines strongly implicated in the fibrogenesis process. Patients in this trial are recruited nationwide and treated and evaluated in the cGVHD Multidisciplinary Program at the National Cancer Institute/National Institutes of Health. In evaluating an exceedingly complex disease with a diverse patient population, cGVHD clinical trials suffer from poor standardization of entry and response-assessment criteria. This has resulted in difficulties in clinical trial data interpretation. Diagnosis and response assessment are based on the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease criteria and is focused on well-defined cGVHD organ manifestations with clearly defined entry, concurrent treatment, and evaluation criteria. To date all patients have met the primary outcome (6 month) endpoint of the trial and will are currently collecting the laboratory and other research study data in preparion of a final manuscript. Lastly, we are exploring the pathways involved in pustular psoriasis and related conditions through a therapeutic protocol using the anti-IL1 therapy anakinra. In this dose escalation study, 30 patients with diverse pustular skin disease manifestations will be treated, along with extensive biological studies exploring mechanism of disease.

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Zhou, Qing; Yang, Dan; Ombrello, Amanda K et al. (2014) Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 370:911-20
Nakrani, Radhika N; Ghosh, Arunima; Richard Lee, Chyi-Chia et al. (2014) New facial papules in a 66-year-old woman with bladder cancer. J Am Acad Dermatol 71:1250-5
Ballester, Leomar Y; Cowen, Edward W; Richard Lee, Chyi-Chia (2014) Adult T-Cell Leukemia-Lymphoma Associated With Follicular Mucinosis. Am J Dermatopathol :
Lim, Young H; Ovejero, Diana; Sugarman, Jeffrey S et al. (2014) Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia. Hum Mol Genet 23:397-407
Kaffenberger, Benjamin H; Zuo, Rena C; Gru, Alejandro et al. (2014) Graft-versus-host disease-associated angiomatosis: a clinicopathologically distinct entity. J Am Acad Dermatol 71:745-53
Pichard, Dominique C; Boyce, Alison M; Collins, Michael T et al. (2014) Oral pigmentation in McCune-Albright syndrome. JAMA Dermatol 150:760-3
McDermott, David H; Liu, Qian; Velez, Daniel et al. (2014) A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor. Blood 123:2308-16
Turegano, Mamina M; Lee, Chyi-Chia R; Malech, Harry L et al. (2014) Recurrent erythematous plaques on sun-exposed sites in an African American boy with chronic granulomatous disease. J Am Acad Dermatol 70:576-80
Spinner, Michael A; Sanchez, Lauren A; Hsu, Amy P et al. (2014) GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood 123:809-21
Naik, Haley B; Cowen, Edward W (2013) Autoinflammatory pustular neutrophilic diseases. Dermatol Clin 31:405-25

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