Adelaide A. Hebert

Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: Genetic and functional analyses

Previously we demonstrated that transgenic mice expressing mutant basal epidermal keratin genes exhibited a phenotype resembling a group of autosomal dominant human skin disorders known as epidermolysis bullosa simplex (EBS). EBS diseases affect approximately 1: 50,000 and are of unknown etiology, although all subtypes exhibit blistering arising from basal cell cytolysis. We now demonstrate that two patients with spontaneous cases of Dowling-Meara EBS have point mutations in a critical region in one (K14) of two basal keratin genes. To demonstrate function, we engineered one of these point mutations in a cloned human K14 cDNA, and showed that a K14 with an Arg-125----Cys mutation disrupted keratin network formation in transfected keratinocytes and perturbed filament assembly in vitro. Since we had previously shown that keratin network perturbation is an essential component of EBS diseases, these data suggest that the basis for the phenotype in this patient resides in this point mutation.

Management of Stevens-Johnson syndrome and toxic epidermal necrolysis in children.

A retrospective analysis of 21 consecutive patients hospitalized with either Stevens-Johnson syndrome or toxic epidermal necrolysis was carried out to assess morbidity and mortality rates and to establish the value of a specific management practice. Fourteen children with Stevens-Johnson syndrome and seven with toxic epidermal necrolysis were cared for at the Childrens Memorial Hospital, Chicago, between 1978 and 1988. All were managed in a well-staffed medical ward or, when necessary, in the pediatric intensive care unit. Supportive measures included reverse barrier isolation, intravenous fluids and nutritional support, meticulous skin care, early detection and treatment of infection, and daily ophthalmologic examination. No patient was treated with systemic steroids. The mortality rate was zero. Eye complications, consisting of dry eyes or mild chronic symblepharon, were the most significant long-term sequelae.

Topical Rapamycin Therapy to Alleviate the Cutaneous Manifestations of Tuberous Sclerosis Complex A Double-Blind, Randomized, Controlled Trial to Evaluate the Safety and Efficacy of Topically Applied Rapamycin

Background and ObjectivesFacial angiofibromas are disfiguring facial lesions, present in up to 80% of patients with tuberous sclerosis complex. Recent elucidation of the complex cell signaling pathways that are disrupted in tuberous sclerosis indicates that rapamycin may be successful in alleviating the appearance of these lesions. The objectives of the current study were to evaluate the safety of topically applied rapamycin in patients with tuberous sclerosis complex and to determine its potential effectiveness in treatment of facial angiofibromas.Patients and MethodsThe study was a prospective, randomized, double-blind, placebo-controlled study performed at the University of Texas Health Science Center at Houston. Study subjects were recruited from the patient populations at the University of Texas Tuberous Sclerosis Center of Excellence. All subjects were over the age of 13 years and had a diagnosis of tuberous sclerosis complex. Subjects were excluded if they were using any form of rapamycin or if they were pregnant. Study subjects applied the study product to their facial angiofibromas nightly for a duration of 6 months. The investigational product contained one of three doses of rapamycin compounded with Skincerity®: (i) no rapamycin; (ii) 1 mg of rapamycin per 30 cc (0.003%); or (iii) 5 mg of rapamycin per 30 cc (0.015%). Plasma rapamycin concentrations were measured monthly to test for systemic absorption. Complete blood counts were performed monthly to test for anemia, neutropenia, or thrombocytopenia. Upon completion of the trial, subjects were asked if the formulation had improved the appearance of their facial angiofibromas.ResultsTwenty-three subjects completed the study. There was no detectable systemic absorption of rapamycin (all blood concentrations were <1.0 ng/mL). There were no significant changes in white blood cell, red blood cell, or platelet counts. Seventy-three percent of subjects in the treatment arms versus 38% of subjects in the placebo arm reported a subjective improvement in the appearance of their facial angiofibromas.ConclusionThe application of low-dose topical rapamycin (0.003–0.015%) to the face can safely decrease the appearance of facial angiofibromas in patients with tuberous sclerosis complex.Trial RegistrationClinicalTrials.gov Identifier: NCT01031901

Neonatal primary cutaneous aspergillosis: case report and review of the literature.

Abstract:  Neonatal primary cutaneous aspergillosis usually presents as an erythematous plaque with pustules that evolve into an eschar. Immunocompromised patients and premature neonates are at risk of developing this disease. Early diagnosis and treatment are critical in preventing progression to a systemic illness. We report a preterm neonate with primary cutaneous aspergillosis and discuss the etiologies, presentations, and treatments for this illness.

Complete Inactivation of the TSC2 Gene Leads to Formation of Hamartomas

The work was supported by National Institutes of Health grant R29NS32300-05 and by a National Tuberous Sclerosis Association Senior Investigator Award (97-4) to H.N.

Kindler syndrome: Report of two cases and review of the literature

Abstract: We evaluated two patients Mrith hereditary bullous polkiloderma. Both had acral buliae, generalized poiidloderma with prominent atrophy, and acral keratoses. One patient, with sporadic disease, hj, in addition, urethral and subgiottic stenoses, weiabing of digits, and poor dentition. Hie other patient, whose disease was dominantiy inherited, had koiionychia. The resuits of cutaneous histopathology, electron microscopy, and immunofiuorescice mapping studies are presented, it is possible that Kindler syndrome and Wearys hereditary acrokeratotic poikiioderma are variants of the same disease.

Treating tinea capitis: Should ketoconazole replace griseofulvin?

We undertook a randomized double-blind comparison of griseofulvin and ketoconazole for the treatment of tinea capitis. The outcome was based on fungal culture results and changes in clinical signs and symptoms determined by an assessment system that yielded a severity score. Patients were evaluated at 4-week intervals for 12 weeks. Seventy-nine patients were enrolled; 46 received griseofulvin, and 33 received ketoconazole. Forty-eight patients (26 griseofulvin, 22 ketoconazole) were considered evaluable. Pathogenic fungi were isolated from 78% of the enrolled and 87% of the evaluable patients. Trichophyton tonsurans was the predominant dermatophyte isolated. Potassium hydroxide preparation correlated poorly with culture results (sensitivity 59%). Of 22 evaluable ketoconazole patients, 16 (73%) were considered to have been treated successfully; 25 of 26 (96%) patients who received griseofulvin were successfully treated (chi-square = 3.54, p less than 0.10). The proportion of culture-positive patients at each follow-up visit appeared somewhat greater for the ketoconazole-treated group than for the griseofulvin-treated group, but the differences were not statistically significant. Analysis of severity scores revealed no significant differences between the groups (t test and Mann-Whitney U test). No significant hepatotoxicity or other adverse reactions were observed. We conclude that griseofulvin should remain the drug of choice for treating tinea capitis.

Serum sickness—like reactions from cefaclor in children

Cefaclor is an oral semisynthetic cephalosporin that is popular in the treatment of infections in children. This drug has been associated with a serum sickness--like reaction characterized by an urticarial eruption, pruritus, arthritis, and/or arthralgias. We report 12 additional cases of cefaclor-related serum sickness--like reactions in children. All patients improved after discontinuation of the drug and no long-term complications resulted.

Tinea capitis caused by Trichophyton tonsurans.

Abstract: Children with tinea capitis caused by Trichophyton tonsurans often have a lifetime of association with the organism and, in spite of intermittent therapy, as adults pass the infection to successive generations. While most current treatment regimens are directed at treating the individual patient, our study supports the need to evaluate and possibly treat all family members and their home environment.

Pityriasis lichenoides in children: Therapeutic response to erythromycin

Fifteen of twenty-two children with pityriasis lichenoides were treated with oral erythromycin. Eleven (73%) had a remission, usually within 2 months. Two others showed partial improvement, and two were unimproved. Seven of the children who experienced a remission were off erythromycin and free of lesions after 2 to 5 months of therapy. A trial of erythromycin as described herein should be considered in children with pityriasis lichenoides before other, possibly more toxic, measures are instituted.