Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature.

Severe cutaneous adverse drug reactions (SCAR) such as the Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DIHS) can be induced by a plethora of medications. The field of pharmacogenomics aims to prevent severe adverse drug reactions by using our knowledge of the inherited or acquired genetic risk of drug metabolizing enzymes, drug targets, or the human leukocyte antigen (HLA) genotype. Dermatologists are experts in the diagnosis and management of severe cutaneous adverse drug reactions (SCAR) in both the inpatient and outpatient setting. However, most dermatologists in the US have not focused on the prevention of SCAR. Therefore, this paper presents a case series and review of the literature highlighting salient examples of how dermatologists can apply pharmacogenomics in the diagnosis and especially in the prevention of SCAR induced by allopurinol and sulfamethoxazole/trimethoprim, two commonly prescribed medications.

An Unusual Case of Morphea in the Setting of Aplastic Anemia.

Cutaneous sclerosis occurs in association with a variety of systemic diseases, including hematologic malignancy, plasma cell dyscrasias, solid organ tumors, and other systemic autoimmune conditions. Herein, we present a unique case of morphea/lichen sclerosus overlap arising in association with aplastic anemia. To expand upon this rare case, we also review the literature surrounding paraneoplastic sclerosing skin disorders. A 53-year-old man presented with a 13-month history of progressive and generalized skin changes. Exam revealed irregular, hypopigmented indurated plaques with focal areas of scale on the bilateral axillae and hips, as well as hyperpigmented brown papules and plaques on the back. Laboratory evaluation revealed pancytopenia and positive anti-nuclear antibody (1:160). Bone marrow biopsy demonstrated hypocellular marrow consistent with aplastic anemia. Furthermore, skin biopsies revealed lichen sclerosus overlying superficial morphea, consistent with a paraneoplastic sclerodermoid-like eruption. While preparations for hematologic-directed therapies were made, skin-directed therapy with a combination topical steroids and topical calcineurin inhibitors was initiated. Eosinophilic fasciitis and scleroderma have been linked to aplastic anemia, and herein, we expand upon this phenomenon by presenting our case of generalized plaque morphea/lichen sclerosus overlap arising in the setting of aplastic anemia. Dermatologists must be aware of this rare association in order to identify precocious hematologic disease.

Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus: report of a case and review of the literature.

Severe bullous eruptions in systemic lupus erythematosus (SLE) patients include bullous SLE, Rowell syndrome, toxic epidermal necrolysis (TEN), and TEN-like eruption of acute cutaneous lupus (TEN-like ACLE). TEN-like ACLE, a rare manifestation of SLE that closely mimics TEN, can be distinguished by characteristic clinical and laboratory findings. A 27-year-old man with SLE who developed TEN-like ACLE after initiating mycophenolate mofetil for active SLE is reported. The reports of 37 women and six men  including our patient with TEN-like ACLE were also reviewed. The diagnosis of SLE or subacute cutaneous lupus erythematosus was either previously confirmed or established at the time of diagnosis of TEN-like ACLE in 41 patients. Fever was present in 59% of patients. The onset of TEN-like ACLE was either subacute (73%) or acute (27%). Thirteen cases did not clarify the nature of disease onset. The skin lesions often presented initially on sun-exposed sites (29 patients) and involved one or more mucous membranes (21 patients). A new medication may have caused the TEN-like ACLE in 67% of the patients. Systemic corticosteroids either alone or combined with hydroxychloroquine, intravenous immunoglobulin, or mycophenolate mofetil were the most commonly used treatment. Patients with TEN-like ACLE patients had an 89% survival.

Birt-Hogg-Dubé Syndrome: A Review of Dermatological Manifestations and Other Symptoms.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant genodermatosis with malignant potential characterized by cutaneous and extracutaneous stigmata. Aberrations in the folliculin (FLCN) gene, which is located on chromosome 17, have been discovered in individuals with this condition. Over 150 unique mutations have been identified in BHD. The skin lesions associated with this condition include fibrofolliculomas, trichodiscomas, perifollicular fibromas, and acrochordons. Extracutaneous features of the syndrome typically include the lung (spontaneous pneumothorax and cysts) and the kidney (neoplasms). The only malignancies associated with BHD are renal cancers; however, other tumors have been observed in individuals with BHD. In this article, the skin lesions associated with this condition are reviewed, lung and renal manifestations associated with this syndrome are presented, and malignancies occurring in these patients are summarized.

Familial Multiple Trichodiscomas: Case Report and Concise Review.

Familial multiple trichodiscomas is a condition characterized by multiple asymptomatic skin papules. The inheritance pattern has not been established. The skin lesions usually appear in childhood. The diagnosis of the cutaneous papules is established by pathologic evaluation. Birt-Hogg-Dubé syndrome is excluded by not detecting any aberration in the folliculin gene locus. Including our patient, 15 index individuals and their families are described. There is no systemic organ involvement or associated malignancies in individuals with this condition.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Concise Review with a Comprehensive Summary of Therapeutic Interventions Emphasizing Supportive Measures.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe dermatologic conditions occurring in the inpatient setting. There is a lack of consensus regarding appropriate management of SJS and TEN. PURPOSE: The scientific literature pertaining to SJS and TEN (subsequently referred to as SJS/TEN) is summarized and assessed. In addition, an interventional approach for the clinician is provided. METHODS: PubMed was searched with the key words: corticosteroids, cyclosporine, etanercept, intravenous immunoglobulin, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The papers generated by the search, and their references, were reviewed. RESULTS: Supportive care is the most universally accepted intervention for SJS/TEN. Specific guidelines differ from the care required for patients with thermal burns. Adjuvant therapies are utilized in most severe cases, but the data are thus far underwhelming and underpowered. Using systemic corticosteroids as sole therapy is not supported. A consensus regarding combined corticosteroids and intravenous immunoglobulin (IVIG) has not been reached. Data regarding IVIG, currently the standard of care for most referral centers, is conflicting. Newer studies regarding cyclosporine and tumor necrosis factor inhibitors are promising, but not powered to provide definitive evidence of efficacy. Data regarding plasmapheresis is equivocal. Thalidomide increases mortality. CONCLUSION: Clinicians who manage SJS/TEN should seek to employ interventions with the greatest impact on their patients' condition. While supportive care measures may seem an obvious aspect of SJS/TEN patient care, providers should understand that these interventions are imperative and that they differ from the care recommended for other critically ill or burn patients. While adjuvant therapies are frequently discussed and debated for hospitalized patients with SJS/TEN, a standardized management approach is not yet clear based on the current data. Therefore, until further data are available, decisions regarding such treatments should be made on a case-by-case basis.