Novel mutation in the fumarate hydratase gene in a patient with Reed syndrome.

Reed syndrome is an autosomal dominant disorder characterized by cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma caused by mutations in the fumarate hydratase gene. Dermatologic evaluation is often the first or only opportunity to discover the diagnosis of Reed syndrome in affected patients, which may prove to be life-saving. We present a 40-year-old woman with history of large uterine leiomyomas who presented with a two-year history of a pruritic papular eruption on the left neck refractory to topical corticosteroids. After histopathologic examination and genetic work-up, the patient was found to have a novel mutation in the fumarate hydratase gene and was subsequently diagnosed with Reed syndrome.

Melanoma and pregnancy.

Herein we analyze three important issues concerning melanoma and pregnancy: 1) While initial case reports and case series predicted a grim prognosis for the woman diagnosed with melanoma during pregnancy, we summarize more recent controlled studies that suggest that pregnancy has no effect on survival in women diagnosed with localized cutaneous melanoma. 2) We review the prognosis for the fetus when a woman is diagnosed with melanoma during pregnancy. While melanoma is the most common malignancy to metastasize to the placenta, metastatic melanoma to the fetus appears to be a rare event. 3) How do we answer questions about future pregnancies and hormonal therapy when counseling women who have been diagnosed with melanoma during pregnancy or the childbearing years? Will future pregnancies worsen prognosis? Based on limited data, pregnancies subsequent to a diagnosis of localized melanoma do not appear to impact prognosis. Are oral contraceptive pills or hormonal replacement therapy contraindicated in these women? Strong epidemiologic evidence suggests that exposure to oral contraceptive pills do not increase the risk for melanoma. Although only a small number of studies have addressed the risk of hormone replacement therapy, the reports demonstrate that this also does not appear to enhance the risk for developing melanoma.

Hormones, nevi, and melanoma: an approach to the patient

For many years, clinicians have been concerned about a potential adverse effect of pregnancy-associated hormones and exogenous hormones on melanocytic nevi and malignant melanoma. Today, these issues are more significant as women have delayed childbearing into their 30's and 40's, and the likelihood of diagnosis with melanoma during pregnancy is enhanced. More recent clinical, epidemiologic, and laboratory studies have shed some light on the relationship among hormones, nevi, and melanoma in pregnancy.

Clinical management of the acute sunburn reaction.

Critical reviews of published human studies about pharmacologic agents used to treat the sunburn reaction show that systemic and topical corticosteroids have little or no clinically important effect on the sunburn reaction. Systemic and topical nonsteroidal anti-inflammatory drugs, when used at dosages to achieve optimal serum levels for anti-inflammatory effect, only result in an early and mild reduction of ultraviolet B-induced erythema. Due to the lack of demonstrated clinical efficacy of these and other medicines to eliminate sunburn or decrease healing time, we currently suggest conservative local symptomatic treatment with adequate pain control until the sunburn naturally resolves.

The relationship of pregnancy, hormones, and melanoma.

There has been considerable interest in the relationship of pregnancy and melanoma. Since 1951, a number of case reports have suggested that pregnancy may induce or exacerbate melanoma. Likewise, there has been concern over the relationship between exposure to oral contraceptives (OCs) or hormone replacement therapy (HRT) and possible increased risk of melanoma. We critically reviewed: (1) controlled clinical trials to assess the effect of pregnancy on the prognosis of melanoma; and (2) epidemiological data to evaluate the risk of melanoma after exposure to OCs or HRT. Pregnancy before, during, or after the diagnosis of melanoma does not appear to influence 5-year survival rates. Exposure to OCs or HRT does not appear to increase the risk of melanoma.

Emergency department management of sunburn reactions.

The medical records of fifteen patients presenting to the emergency department of a university hospital for sunburn were reviewed. Patients with sunburn had a mean age of 27 years and injury was most likely to occur in July. Six patients had blisters secondary to the ultraviolet injury. Treatment with nonsteroidal anti-inflammatory drugs was used for nine of fifteen patients. Although eight instances of patient education about the primary prevention of future sunburn were documented in the medical records, only one patient record had documentation of her being warned about her increased risk for skin cancer.

Acanthosis nigricans.

Acanthosis nigricans is a lesion affecting localized areas of the skin in persons with obesity and/or hyperinsulinemia. Roughening of the skin correlates with histological papilomatosis and the apparent darkening is due to hyperkeratosis. Biochemical mechanisms for developing this hyperplastic lesion are unclear, but likely involve local cutaneous growth factors. Cross sectional surveys of unselected populations have demonstrated that young children have low prevalences of obesity and acanthosis nigricans, but the prevalences of both increase with increasing age until plateaus are reached after the age of ten. Nearly 40% of Native American teenagers have acanthosis nigricans, whereas about 13% of African American, 6% of Hispanic, and less than 1% of white, non-Hispanic children aged 10-19 have clinically apparent acanthosis nigricans. We conclude that the presence of this skin lesion is a clinical surrogate of laboratory-documented hyperinsulinemia. Acanthosis nigricans identifies a subgroup within an ethnic group who have the highest insulin concentration, the most severe insulin resistance, and thus the highest risk for the development of type 2 diabetes.

Changes in size of melanocytic nevi during pregnancy.

BACKGROUND: The relation between pregnancy, melanocytic nevi, and malignant melanoma is ambiguous. It has been reported that nevi grow and darken during pregnancy. Several recent studies have shown that malignant melanomas diagnosed during pregnancy are thicker than those not associated with pregnancy. This may be partially due to a delay in diagnosis because of the opinion that benign nevi change during pregnancy. OBJECTIVE: Our purpose was to photographically document any change in size of melanocytic nevi during pregnancy. METHODS: Twenty-two women were entered into the study during the first trimester of pregnancy and examined again in the third trimester. All nevi 2 mm or larger on their back were documented and photographed. Photographs were then compared and nevi measured for change in diameter. RESULTS: Of 129 nevi, only eight nevi (6.2%) changed in diameter from the first to the third trimester. The mean change in size of all nevi studied was zero. Of the eight nevi that did change in size, four increased by 1 mm and four decreased by 1 mm. CONCLUSION: Our study suggests that pregnancy is not associated with any significant change in size of melanocytic nevi. Patient characteristics (age, pregnancy number, skin type) and nevi characteristics (location, number) did not correlate with any change in size.

Pregnancy and the prognosis of malignant melanoma.

The influence of pregnancy on the prognosis of malignant melanoma (MM) is unclear. Since 1951, a number of case reports have suggested that pregnancy may have an adverse effect on the clinical course of MM. We reviewed the literature on pregnancy and MM and focused on the well-controlled studies. Based on a limited number of controlled trials, pregnancy before, after, or during the time of diagnosis of stage 1 MM does not appear to affect survival. However, these data should be interpreted with caution because the duration of follow-up and number of patients may not be sufficient to observe a true effect.

Severe adverse cardiovascular effects of pulse steroid therapy: is continuous cardiac monitoring necessary?

Pulse steroid therapy (PST) has been used in dermatology to treat a variety of severe inflammatory disorders. Dermatologists have usually recommended that patients be hospitalized for continuous cardiac monitoring during PST administration, although specialists in other fields have administered PST in an outpatient setting. We reviewed the literature concerning serious adverse cardiovascular effects of PST. These were rare and have been mainly reported in nondermatologic patients, typically those with kidney or heart disease. Although outpatient administration of PST may be a safe practice for some dermatologic patients, we cannot make a firm recommendation without a prospective trial.

Delusional parasitosis: a dermatologic, psychiatric, and pharmacologic approach.

Delusional parasitosis is a syndrome in which the patient has the false belief that he is infested by parasites. Although this is a psychiatric disorder, patients usually seek care from dermatologists. DP has various causes. It may occur as the sole psychologic disturbance, or it may be associated with an underlying psychiatric disorder or physical illness. A dermatology-psychiatry liaison is advocated for establishing a viable differential diagnosis and selecting appropriate therapy. The antipsychotic agent pimozide is currently the most effective treatment when DP occurs as an encapsulated delusion. Pimozide therapy requires careful monitoring because this drug has several potentially serious adverse effects, and relapse often occurs on discontinuation of the drug.

Does pregnancy influence the prognosis of malignant melanoma?

The effect of pregnancy on the clinical course of malignant melanoma (MM) is unclear. Early clinical and laboratory evidence suggested a relation between hormones and MM and subsequently between pregnancy and MM. We reviewed the literature on MM and pregnancy to address three questions: What is the effect on prognosis if an MM is diagnosed during pregnancy? What is the effect of previous pregnancies on the prognosis of MM? What effect does a subsequent pregnancy have on the prognosis of MM? On the basis of a limited number of controlled studies, it does not appear that being pregnant before, after, or at the time of diagnosis of stage I MM influences the 5-year survival rate. However, caution in interpreting these data must be taken because it is possible that the duration of follow-up and size of the study populations are not sufficient to observe a true effect.

Long-term oral antibiotics for acne: is laboratory monitoring necessary?

BACKGROUND: The role of laboratory monitoring in patients receiving long-term oral antibiotics for acne vulgaris has not been clearly defined. OBJECTIVE: The purpose of our study was (1) to evaluate the literature for objective evidence on the value of routine laboratory monitoring of the asymptomatic patient receiving oral antibiotics for acne and (2) to determine the utilization of laboratory monitoring of these patients by Connecticut dermatologists. METHODS: We surveyed Connecticut dermatologists by phone and inquired about the laboratory monitoring performed in patients receiving long-term oral tetracycline, minocycline, or erythromycin for acne. RESULTS: Eight published studies reported a total of 777 patients who had laboratory monitoring at various frequencies while receiving oral antibiotics for acne. Only one adverse drug reaction (ADR) was detected in a patient in whom mild hyperbilirubinemia developed. Of the 75 Connecticut dermatologists who participated in our survey, 48 (64%) perform some laboratory monitoring; 29% do so routinely, and 35% under special circumstances. CONCLUSION: Our literature review does not support routine laboratory monitoring in all patients who receive long-term oral antibiotics for acne; rarely does such screening detect an ADR and thus does not justify the cost of such testing. A relatively small proportion of Connecticut dermatologists check laboratory tests more frequently than appears necessary; in our opinion, laboratory monitoring should be limited to patients who may be at higher risk for an ADR.

Longitudinal evaluation of polymorphonuclear leukocyte chemiluminescence in premature infants.

A chemiluminescence (CL) microassay was used to evaluate polymorphonuclear leukocyte (PMN) function in premature newborn infants longitudinally during a 2-month period and in healthy adult control subjects. At postnatal ages of 12, 26, 40 and 54 days the infants' mean peak CL activity was significantly lower than that of the adults. Infants with one or more low CL responses were more severely ill than those with normal CL activity. The infants with low CL responses had longer hospital stays and a higher frequency of serious infections, as well as more days of level 3 care, antimicrobial therapy, supplemental oxygen, assisted ventilation, and total parenteral nutrition. The PMN CL activity before, during, and after episodes of serious infection did not differ. In addition, a high frequency of depressed CL activity was observed at the time of infection. Our findings are consistent with previous studies suggesting that defective PMN oxidative metabolic responses are more common in neonates undergoing stress. Our results further suggest that defective PMN function may persist for the first 2 months of life and during the course of serious infection. Enhancement of PMN host defense may be an important strategy in the management of neonatal sepsis.

Evaluation of theophylline pharmacokinetics in a pediatric population using mixed effects models.

Routine clinical pharmacokinetic data collected prospectively from pediatric patients receiving theophylline were analyzed using the NONMEM (nonlinear mixed effects model) digital computer program. A total of 314 measured serum theophylline concentrations (STCs) were obtained from 84 hospitalized patients ranging in age from 4 months to 15.2 years with the majority of patients between the ages of 1 and 8 years. Fifty-six percent were male. The race/ethnicity distribution was 71.4% Latin, 15.5% black, 11.9% Caucasian, and 1.2% (one subject) Pakistani. Of the total number of observed STCs, 16.2% reflected some degree of outpatient dosing. The pharmacokinetic model used was a one-compartment open model with either zero-order or first-order absorption and first-order elimination. Age was the most important determinant of theophylline clearance (Cl); weight was inferior to age and did not statistically improve the model (p greater than 0.005) when combined with age. Total Cl increased by 10%/year over the age range of 1 to 15 years of age. Black race and male gender were associated with higher Cl values: for a given age, Cl was 34% higher for blacks than the reference population composed of the remaining patients, and Cl for males was 25% higher than that for females. The volume of distribution (Vd) for the population was estimated to be 0.62 L/kg. The interindividual variability in Cl and Vd expressed as coefficients of variation were 19 and 28%, respectively. The residual intraindividual error variance corresponded to a standard deviation of 2.8 micrograms/ml. The STCs that represented some degree of outpatient dosing were 21% lower than those reflecting only inpatient dosing. Alternate models that include weight as a determinant of theophylline clearance are also provided. The NONMEM method of determining population pharmacokinetics is well suited to the pediatric population since it does not require a large number of STCs per patient. In this study a mean of only 3.7 STCs per patient were utilized to provide information which should prove useful in the design and adjustment of theophylline dosage regimens in children.

Luminol-dependent chemiluminescence microassay for phagocytic function.

A luminol-dependent chemiluminescence (CL) microassay was developed to measure phagocytic function of peripheral blood leukocytes. Buffy coats, obtained by centrifugation of only 100 microliter of whole blood, provided an enriched population of polymorphonuclear leukocytes (PMNs). The total reaction mixture, consisting of leukocytes-luminol-inducer (opsonized zymosan), was 450 microliter. Peak CL activity was seen 5 min after addition of inducer at 37 degrees C with cells tested within 60 min after collection. Tests to determine precision and reproducibility of the microassay gave a coefficient of variation of 8.5% and 11%, respectively. There was no significant difference between the mean peak CL values for 20 healthy adult donors compared to 14 premature neonates, however, the newborns' CL activity declined more rapidly; CL activity was severely depressed in cells obtained from a patient with chronic granulomatous disease. Results suggest that this microassay provides a simple, rapid, and reliable test of phagocytic function in cases where the amount of blood available for testing is limited.