Paediatric pseudoxanthoma elasticum with cardiovascular involvement.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is characterized by aberrant mineralization of connective tissues, causing considerable morbidity and mortality. The disease is typically of late onset, the skin manifestations first being noted in the teens or later. Another aberrant mineralization disorder, generalized arterial calcification of infancy (GACI), is present at birth and can demonstrate a phenotypic overlap with PXE. OBJECTIVES: A patient with PXE was noted to have skin findings as early as at 6 years of age, with cardiovascular involvement. The purpose of this study was to examine the genetic basis of this phenotypic presentation in the spectrum of PXE/GACI. METHODS: The patient's genotype was studied by sequencing ABCC6 and ENPP1, genes known to be associated with PXE and/or GACI. RESULTS: Screening of the ABCC6 gene revealed two pathogenetic mutations, p.R1141X and g.del23-29. Analysis of the ENPP1 gene failed to demonstrate the presence of mutations. CONCLUSIONS: This study demonstrates the presence of cutaneous findings of PXE in an 8-year-old paediatric patient, with cardiovascular involvement, illustrating the phenotypic spectrum of PXE.

A novel rat model for chemotherapy-induced alopecia.

BACKGROUND: More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. AIM: To develop a clinically relevant adult rat model for CIA. METHODS: We first tested whether neonatal pigmented Long-Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle, and starting 15 days later, the rats were treated with etoposide for 3 days. RESULTS: Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation. CONCLUSIONS: A novel, pigmented adult rat model has been established for CIA. By hair-shaft clipping during early telogen, synchronized anagen entry was induced, which resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA, and will be a useful tool to test agents for the prevention and treatment of CIA.

tert-butyl hydroperoxide, an organic peroxide, causes temporary delay in hair growth in a neonatal rat model.

tert-butyl hydroperoxide (tBHP), an organic peroxide, has been shown to cause irreversible damage to keratinocytes in vitro with prolonged administration at high concentrations, and reversible damage with short-term administration at low concentrations. To investigate the effects of tBHP on keratinocytes in vivo, we analysed hair growth in tBHP-treated neonatal rats. Sprague-Dawley and Long-Evans rat pups were injected subcutaneously with tBHP or vehicle once daily for 6 days, and hair growth was monitored. The tBHP-treated rats had a significant delay in hair growth. However, this delay reversed within days, and the hair coats, including hair pigmentation, of tBHP-treated and sham-treated rats were indistinguishable 2 weeks later. Histological analysis and BrdU labelling of S phase cells confirmed the delay in hair-follicle growth and its reversal in tBHP-treated rats. Our results indicated that the changes incurred in hair follicles by short-term use of high-dose oxidants in vivo are temporary and reversible.

IgA antibodies in chronic bullous disease of childhood react with 97 kDa basement membrane zone protein.

Chronic bullous disease of childhood (CBDC) is an autoimmune blistering disease occurring in prepubertal children. Both CBDC and its adult counter-part, linear IgA bullous dermatosis (LABD), are characterized by linear deposition of IgA along the cutaneous basement membrane zone (BMZ). Circulating IgA antibody in LABD has been found to bind to a 97-kDa BMZ antigen, whereas the antigen in CBDC has not been well characterized. The purpose of this study was to evaluate the immunoreactivity of BMZ IgA antibodies in a series of CBDC patients. We evaluated 12 sera from patients with CBDC with circulating IgA anti-BMZ antibodies on indirect immunofluorescence (IIF), which stained the epidermal side of split skin with titers ranging from 1:20 to 1:640. Immunoblotting was performed against two preparations of BMZ proteins: one enriched with the two bullous pemphigoid antigens (BP230, BP180) and one enriched with the LABD antigen (LABD97). Eight of the twelve sera reacted with a 97-kDa protein that co-migrated with the protein detected in many LABD sera. The intensity of the reaction on immunoblot correlated with serum antibody titers. There was no consistent pattern of reactivity of the IgA anti-BMZ antibodies with either the BP230 or BP180 antigens, although two sera reacted with several higher molecular mass proteins (160-200 kDa). The significance of this reactivity was examined with immunoblotting using BMZ-affinity-purified antibodies, and ELF using nitrocellulose-eluted antibodies. One serum also contained anti-BMZ IgA antibodies that reacted with a 180-kDa protein, corresponding to BP180. We conclude that IgA antibodies in CBDC sera recognize a 97-kDa BMZ antigen present on the epidermal side of BMZ split skin that co-migrates with the antigen previously identified in LABD. These findings suggest that CBDC and LABD are the immunologically related disorders occurring in different age groups.

Childhood bullous pemphigoid. Clinical and immunologic features, treatment, and prognosis.

A 2 1/2-month-old female infant presented with multiple tense bullae on the hands and feet. Analysis of biopsy specimens confirmed our clinical impression of childhood bullous pemphigoid. Confirmatory data included type IV collagen mapping of the basement membrane zone, a readily available technique that helps distinguish childhood bullous pemphigoid from childhood epidermolysis bullosa acquisita. To our knowledge, our patient is the youngest described with childhood bullous pemphigoid, and we use this opportunity to review the literature and examine the clinical and immunologic features, treatment, and prognosis of this rare childhood immunobullous disorder.

Dermatologic consultations in the hospital setting.

BACKGROUND AND DESIGN: Dermatologic practice occurs mainly in the outpatient setting. The reasons for, frequency, and impact of inpatient dermatologic consultation are largely unstudied. In this report, we prospectively studied dermatologic consultation in the major teaching hospital complex of a medical school. Over a period of 8 months, we prospectively recorded the demographics of the patients for whom consultation was requested, the provisional dermatologic diagnosis of the referring service, the final diagnosis of the dermatologic service, and the tests necessary to arrive at a final diagnosis. RESULTS: During a period of slightly over 8 months, dermatologic consultation was requested and delivered to 591 patients who were either hospitalized or being evaluated in the emergency department or other urgent care settings. The services requesting consultation most frequently were medicine (39%), pediatrics (14%), surgery (12%), psychiatry (6%), and neurology (3%). In 51% of consultations, the patients were younger than 45 years of age. Diagnostic tests, including Tzanck smear and potassium hydroxide preparation, confirmed the clinical diagnosis in up to 50% of cases. Dermatologic consultation changed dermatologic diagnosis and treatment in more than 60% of the patients. Generally, the dermatologic diagnoses most frequently missed by the referring service were common conditions with established treatment. CONCLUSIONS: Dermatologic consultation in the hospital setting improves dermatologic diagnosis and has an impact on treatment.

The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara variant, a subtype of EB, is characterized by widespread blister formation that may include the oral cavity and nails. Many patients with the Dowling-Meara phenotype are at increased risk of sepsis and death during infancy. The treatment of EB is generally supportive. The tissue-engineered skin used (Apligraf) is a bilayered human skin equivalent developed from foreskin. It is the only Food and Drug Administration-approved skin equivalent of its kind. It is approved for the treatment of venous ulcers of the lower extremities. It has also been used to treat acute wounds, such as graft donor sites and cancer excision sites. OBSERVATION: To our knowledge, we describe the first case in which a newborn with EB, Dowling-Meara variant, was treated with bilayered tissue-engineered skin. The areas treated with the tissue-engineered skin healed faster than the areas treated with conventional therapy. Most of the areas treated with tissue-engineered skin have remained healed, without developing new blisters. These areas appear to be more resistant to trauma. CONCLUSIONS: Our early success with tissue-engineered skin in this patient may have a significant impact on the future treatment of neonates with EB simplex. Future studies are needed to determine if the beneficial effects of tissue-engineered skin are reproducible in other neonates with EB simplex and in patients of all ages with different subtypes of EB.

Childhood systemic lupus erythematosus. Association with pancreatitis, subcutaneous fat necrosis, and calcinosis cutis.

Pancreatitis developed in a 12-year-old girl with a one-year history of systemic lupus erythematosus. The pancreatitis was first manifested by panniculitis of the lower extremities. Calcinosis cutis subsequently developed, both in areas of panniculitis and in areas free of panniculitis. The patient's medications at the time of onset of pancreatitis included prednisone, hydrochlorothiazide, and azathioprine, all of which have been reported to be causes of pancreatitis. We wish to alert physicians that pancreatitis associated with cutaneous panniculitis and calcinosis cutis may develop in children with systemic lupus erythematosus.

Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds.

BACKGROUND: At present, wound treatment of inherited epidermolysis bullosa (EB) is only supportive. OBJECTIVE: To determine the safety and clinical effects of tissue-engineered skin (Apligraf; Organogenesis Inc, Canton, Mass) in the healing of wounds of patients with different types of EB. DESIGN: An open-label uncontrolled study of 15 patients with EB treated with tissue-engineered skin. Each patient received tissue-engineered skin on up to 2 wounds on each of 3 clinic visits: day 1, week 6, and week 12. They were evaluated 7 (+/- 3) days and 6 weeks after each round of treatment. A quality-of-life survey was administered during week 6. SETTING: University of Miami, Miami, Fla. PATIENTS: Volunteers with EB. MAIN OUTCOME MEASURE: Safety and wound healing. RESULTS: A total of 69 different acute wounds received tissue-engineered skin at the day-1 (24 wounds), week-6 (23 wounds), and week-12 (22 wounds) visits. Overall, 63 wounds (79%) were found healed at the day-7 visit. Of the acute wounds, 82% (51/62) were healed 6 weeks after being treated, 75% (27/36) after 12 weeks, and 79% (11/14) after 18 weeks. Nine chronic wounds were also treated. Four were healed at 6 weeks; however, 7 were still open at the last clinic visit (week 18). There were no signs of rejection or clinical infection and no adverse events related to the tissue-engineered skin. The quality of life for most patients improved after treatment. Compared with patients' recollection of wounds treated with standard dressings, healing was faster and less painful. CONCLUSION: In this series of patients, tissue-engineered skin induced very rapid healing, was not clinically rejected, and was devoid of adverse effects. It was felt by the patients and families to be more effective than conventional dressings for EB wounds.

Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance.

BACKGROUND: Kwashiorkor is the edematous form of protein-energy malnutrition. It is associated with extreme poverty in developing countries and with chronic malabsorptive conditions such as cystic fibrosis in developed countries. Rare cases of kwashiorkor in affluent countries unrelated to chronic illness have been reported. We present 12 cases of kwashiorkor unrelated to chronic illness seen over 9 years by pediatric dermatologists throughout the United States, and discuss common causative themes in this easily preventable condition. OBSERVATIONS: Twelve children were diagnosed as having kwashiorkor in 7 tertiary referral centers throughout the United States. The diagnoses were based on the characteristic rash and the overall clinical presentation. The rash consisted of an erosive, crusting, desquamating dermatitis sometimes with classic "pasted-on" scale-the so-called flaky paint sign. Most cases were due to nutritional ignorance, perceived milk intolerance, or food faddism. Half of the cases were the result of a deliberate deviation to a protein-deficient diet because of a perceived intolerance of formula or milk. Financial and social stresses were a factor in only 2 cases, and in both cases social chaos was more of a factor than an absolute lack of financial resources. Misleading dietary histories and the presence of edema masking growth failure obscured the clinical picture in some cases. CONCLUSIONS: Physicians should consider the diagnosis of kwashiorkor in children with perceived milk allergies resulting in frequent dietary manipulations, in children following fad or unorthodox diets, or in children living in homes with significant social chaos. The presence of edema and "flaky paint" dermatitis should prompt a careful dietary investigation.

Ten days of orotracheal intubation with successful extubation in an infant with junctional epidermolysis bullosa.

OBJECTIVE: The most severe form of generalized junctional epidermolysis bullosa, the Herlitz variant, is associated with a number of extracutaneous manifestations. We report on a 45-day-old infant with laryngotracheobronchial mucosa involvement who underwent successful tracheal extubation after 10 days of orotracheal intubation and mechanical ventilatory support. Issues regarding airway management and mechanical ventilatory support in the pediatric intensive care unit are discussed.

Diagnosis and treatment of childhood scabies and pediculosis.

Human scabies infestations are still a widespread occurrence. This article discusses the clinical features, infections, lesions, and sites of involvement of different types of scabies as well as pediculosis.

Screening for psychosocial dysfunction in pediatric dermatology practice.

The Pediatric Symptom Checklist, a brief psychosocial screening questionnaire, was used in a multi-center study of pediatric dermatology clinics (n = 377). Overall rates of positive screening indicated that approximately 13% of patients screened positive, a rate similar to findings in primary care pediatric settings. Examining the sample in greater detail demonstrated that children whose dermatologic disorder is perceived to have a greater impact on their appearance are at higher risk for psychosocial dysfunction.

Scabies. How to find and stop the itch.

Scabies is a pruritic skin infestation caused by the itch mite Sarcoptes scabiei. Physical proximity allows the mite to move from one host to another. The diagnosis is made by identifying the mite or its eggs or excrement microscopically from a sample of skin scrapings. Treatment is achieved with topical application of a scabicide and elimination of the mite from the patient's surroundings.

Localized scleroderma or morphea?

Morphea is a frequently mild, benign, and self-limiting skin disease with a less than 1% reported chance of progressing to systemic scleroderma. Morphea is a sufficient and less terrifying name for these disorders than localized scleroderma.