Psychological disturbance in atopic eczema: the extent of the problem in school-aged children.

Although psychological factors are widely considered to be important in atopic eczema, there have been few controlled studies to assess the extent of disturbance in affected children and the problems experienced by their parents. This study was designed to find out the degree of psychological difficulty experienced by children with atopic eczema, whether their mothers show higher levels of mental distress than a comparison group, and whether the families of children with atopic eczema have less social support than the comparison group. We investigated 30 school-aged children with atopic eczema for psychological problems using the Rutter parent scale and compared them with 30 children with relatively minor skin lesions such as viral warts. Mental distress in mothers was assessed using the General Health Questionnaire. The Family Support Scale was used to get a measure of the social support experienced by the families. We found twice the rate of psychological disturbance in children in the eczema group compared with the control group. This difference was statistically significant for children with moderately severe eczema and severe eczema, but not for children with very mild eczema. Levels of mental distress were no greater in mothers of children with eczema than in parents of the control group and there was no difference in the degree of social support experienced by their families. These findings indicate that school-aged children with moderate and severe atopic eczema are at high risk of developing psychological difficulties, which may have implications for their academic and social development.

p53 immunoreactivity in non-melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours.

p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 dysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).

Increased prevalence of dysplastic and malignant lip lesions in renal-transplant recipients.

BACKGROUND: Renal-transplant recipients are known to have increased rates of skin cancer associated with exposure to the sun. Little is known, however, about the prevalence and histologic features of lesions of the lips in these patients, or about risk factors for such lesions. METHODS: We examined the lips of 160 renal-transplant recipients (105 men and 55 women; mean [+/- SD] age, 48 +/- 13 years) and 160 normal subjects matched with the transplant recipients for age, sex, and skin type. The mean length of time between transplantation and the examination was 69 +/- 52 months; 58 percent of the recipients had received their grafts more than 60 months earlier. RESULTS: Among the 160 renal-transplant recipients, 21 (13 percent) had leukoplakia; in 2 (1.2 percent) the leukoplakia contained squamous-cell carcinoma. In contrast, only one normal subject (0.6 percent) had leukoplakia. Histologically, 13 of the 21 leukoplakias (62 percent) in the renal-transplant recipients who underwent biopsy were dysplastic, and 2 (10 percent) contained squamous-cell carcinoma. Actinic change was evident in 91 percent of the dysplastic lesions but not in the nondysplastic lesions (P < 0.001). Exposure to the sun and smoking were risk factors for dysplastic and malignant lip lesions in the renal-transplant recipients (P < 0.001 and P = 0.003, respectively). Among these recipients, only men had dysplastic or malignant lip lesions (P = 0.006); lipstick was used frequently by 73 percent of the women. The clinical appearance of lip lesions did not predict the presence of dysplasia or cancer. CONCLUSIONS: Renal-transplant recipients have an increased prevalence of leukoplakia, dysplasia, and cancer of the lip.

Cutaneous warts and tumours in immunosuppressed patients.

As increasing numbers of recipients of renal allografts survive long term, complications of prolonged immunosuppression have become apparent. Of particular concern are the high rates of non-melanoma skin cancer (NMSC) and carcinoma of the cervix, vulva and perineum.

Skin cancer and warts in immunosuppressed renal transplant recipients.

Non-melanoma skin cancer (NMSC) is increasingly recognised as a complication of long-term immunosuppression and has been particularly studied in renal transplant recipients (RTR). A population study of renal transplant recipients has been performed with analysis of those features contributing to a high rate of detection of NMSC, such that 40% patients with fair skin have NMSC 5 years after transplantation. 90% of the total patient population have warts 5 years after transplantation, many being atypical and in sun-exposed sites. Therefore, contributory factors in these patients include not only the global immunosuppression, ultraviolet radiation (UVR)-induced mutagenesis and photoimmunosuppression, but also the widespread presence of human papillomavirus (HPV) infection, including the unusual epidermodysplasia verruciformis (EV)-associated cutaneous oncogenic HPV.

Prevalence and risk factors associated with leukoplakia, hairy leukoplakia, erythematous candidiasis, and gingival hyperplasia in renal transplant recipients.

The aims of this study were to determine the prevalence of intraoral lesions in renal transplant recipients and to identify possible risk factors. The oral mucosa of 159 renal transplant recipients and 160 control patients was examined. The most common lesion in renal transplant recipients was cyclosporin-induced gingival hyperplasia (prevalence 22%) and patients with gingival hyperplasia were found to be taking significantly more cyclosporin-A than those without (p < 0.001). The prevalence of hairy leukoplakia and leukoplakia in renal transplant recipients was 11.3% and 10.7%, respectively, compared with 0% and 5.6% in the controls. Oral candidiasis was observed in 9.4% of renal transplant recipients compared with 2.5% of the controls; 3.8% of renal transplant recipients exhibited erythematous candidiasis, but this was not seen in the controls. Renal transplant recipients had a significantly increased risk of developing gingival hyperplasia (p < 0.0001), oral candidiasis (p < 0.0005), and two other conditions that have a well-established association with the immune suppression accompanying HIV infection, hairy leukoplakia (p < 0.0001) and erythematous candidiasis (p < 0.01).

Non-melanoma skin cancer in renal transplant recipients: the extent of the problem and a strategy for management.

Over the past 2 years, we have examined all patients with a functioning renal allograft attending a regional nephrology unit. A total of 291 patients were examined. 172 (59%) were found to have cutaneous warts, and 64 (21.9%) had non-melanoma skin cancer (NMSC). The proportion of patients with both warts and NMSC increased with time from transplantation: 40% of patients who had been transplanted for more than 9 years had NMSC. Fifteen patients had extensive dysplastic change in all sun-exposed areas, particularly the dorsal aspect of the hands. This subgroup of patients develop large numbers of tumours, particularly squamous cell carcinomas (SCC), and require close surveillance and frequent surgery. One patient has died as a result of rapidly evolving metastases from an SCC on the dorsum of the hand. Excision and grafting of the backs of the hands in four patients, and long term etretinate therapy in 6 patients have led to a marked reduction in the frequency of surgery to remove tumours. The very high rate of NMSC, frequently multiple, found in this study of UK residents is a source of concern and indicates the need for close dermatological monitoring of allograft recipients, with intensive surveillance of patients with extensive dysplasia, who may develop tumours requiring surgery every few weeks.

Keratin 17 expression as a marker for epithelial transformation in viral warts.

The profile of keratin expression in benign warts from various cutaneous and mucosal sites along with dysplastic warts and squamous cell carcinomas has been examined using a panel of monospecific antibodies to epithelial keratins. Viral warts and verrucous keratoses from immunosuppressed renal transplant recipients show a spectrum of squamous atypia from benign lesions, from minimal changes to full thickness dysplasia. Changes associated with malignancy include loss of differentiation-specific keratins 1 and 10 together with expansion of basal cell epitopes and inappropriate expression of simple epithelial keratins 8, 18, and 19 in advanced squamous cell carcinoma. This late expression of keratins 8 and 18 contrasts with early expression of keratin 17 in all dysplastic lesions examined. Keratin 17 is found suprabasally in hyperproliferative lesions, including benign warts, but marked basal plus suprabasal expression is seen increasingly in malignantly transformed epidermis. These findings were not specific to immunosuppression, as shown by identical findings in control squamous cell carcinoma from nonimmunosuppressed individuals. Keratin 17 expression may prove prognostically helpful when assessing dysplasia in epidermal tumors.

Malignant transformation of cutaneous lesions in renal allograft patients: a role for human papillomavirus.

Renal allograft recipients are at greatly increased risk of developing squamous cell carcinomas. As these frequently arise adjacent to areas of multiple viral warts, we have investigated a possible role for human papillomavirus in malignant transformation within this population. We established, as primary cultures, keratinocytes from 24 lesions of varying degrees of squamous atypia from 9 patients. Ten of 14 cultures screened for the presence of episomal human papillomavirus DNA were positive using a mixed probe for cutaneous human papillomaviruses, although episomal copy was universally lost with continued passage. Three cultures, 2 of which were derived from malignant tissue and 1 from a benign lesion, were positive when screened with a probe for potentially oncogenic human papillomavirus DNAs 5 or 8. Both positive cultures of malignant origin exhibited extended lifespan and have been briefly characterized by morphology and growth requirements.

HLA antigen frequencies in renal transplant recipients and non-immunosuppressed patients with non-melanoma skin cancer.

An increased frequency of human leukocyte antigen (HLA)-DR1 was found in 49 non-immunosuppressed patients with non-melanoma skin cancer (NMSC), being highest in patients under the age of 60 with multiple squamous cell carcinomas (SCC). Of 266 patients receiving long-term immunosuppression following renal transplantation 46 (17%) were found to have NMSC. No increase in HLA-DR1 was found in renal transplant recipients (RTR) with non-melanoma skin cancer (RTR+C) when compared with matched renal transplant recipients without skin cancer (matched RTR-C), or when compared with healthy controls. There was an increased frequency of DQw2 in RTR+C, most pronounced in RTR with SCC (61.9% compared with 18.75% in matched RTR-C), giving a relative risk of 13.98. We found statistically significant differences in the frequency of a number of HLA antigens on comparing RTR+C with healthy controls, but none of these differences were found when we compared RTR+C against matched RTR-C.

Clinical, histologic, and ultrastructural findings in two cases of infantile systemic hyalinosis.

Two unrelated infants had stiff skin and painful joint contractures in the first few months of life. Other features included gingival hyperplasia, small papules on the face and trunk, perianal nodules, and bloody diarrhea. Hyaline material was evident in the papillary dermis and gut mucosa in both patients. Ultrastructural examination revealed a distinctive fibrillogranular appearance. These infants have the same clinical, histologic, and ultrastructural features as four infants we reported previously with infantile systemic hyalinosis. One of the patients described here demonstrated some features that overlap with those of juvenile hyaline fibromatosis.

A double-blind controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with atopic eczema.

A double-blind controlled trial of hyposensitization with tyrosine-adsorbed Dermatophagoides pteronyssinus vaccine in 24 children with atopic eczema and immediate hypersensitivity to D. pteronyssinus failed to demonstrate superiority over placebo after a standard 8 month course of treatment. In a second phase, children initially administered active treatment were randomly allocated to continue with active treatment or switched to placebo for a further 6 months. The clinical scores suggest that prolonged hyposensitization may be more effective than placebo but the numbers were too small to permit confident conclusions. A dramatic placebo effect may have served to conceal any additional therapeutic effect from active treatment.

Subcutaneous fat necrosis in two infants after hypothermic cardiac surgery.

Two infants experienced subcutaneous fat necrosis (SCFN) at a relatively late age after cardiac surgery with induced hypothermia. The condition resolved in both patients over four weeks without treatment. The appearance of SCFN after the newborn period is very unusual, and in these patients was probably related to the hypothermia.

Infantile systemic hyalinosis: newly recognized disorder of collagen?

Four infants with stiff skin and painful joint contractures in the first few months of life are described. Other features included small papules, particularly on the face and trunk, perianal nodules, hyperpigmentation over the metacarpophalangeal joints and over the malleoli, gingival hyperplasia, persistent diarrhea, and failure to thrive. Two of these infants died before the age of 18 months. In each case hyaline material was found in the papillary dermis. Ultrastructurally, there was a distinctive fibrillogranular appearance in which a banding pattern could be observed. This material was also found within membrane-bound vacuoles in macrophages and fibroblasts. It had an appearance and localization identical with that of collagen type VI. These features are similar to those reported in juvenile hyaline fibromatosis. It is believed that these infants have a closely related, but nonetheless distinctive, inherited disorder of collagen.

Michelin-tire baby syndrome resulting from diffuse smooth muscle hamartoma.

We cared for an infant who was born with the Michelin-tire baby syndrome characterized by dermatomegaly and hypertrichosis. Histology revealed a diffuse smooth muscle hamartoma.

Hypomelanosis of Ito: spectrum of the disease.

Nineteen children with hypomelanosis of Ito are described. Fourteen were developmentally delayed and nine had a history of seizures. Hemihypertrophy was present in four patients, syndactyly in three, and scoliosis in one. Twelve of the children had abnormal electroencephalograms and nine had abnormal brain scans, four with appearances suggestive of abnormal neuronal migration. There is very little evidence, either from the literature or from our patients, that the disease is inherited. The pattern of the cutaneous lesions suggests that the condition may result from the presence of two different cell populations as a result of mosaicism.

The role of psoralen photochemotherapy (PUVA) in the treatment of severe atopic eczema in adolescents.

Fifteen adolescent children with severe, persistent atopic eczema were treated with oral psoralen photochemotherapy (PUVA). This resulted in initial clearance of eczema in 14 of the 15 children, nine of whom achieved a remission. Apart from its effectiveness, a major benefit of this therapeutic approach was that it was associated with resumption of normal growth in children who were previously growing poorly, either as a direct result of severe eczema or its treatment. Nevertheless, against the considerable advantages of PUVA for this group of patients have to be balanced the possible hazards, because relatively high exposures are required in some individuals, both initially to induce clearance and subsequently to maintain it.

Transient zinc deficiency in two full-term breast-fed siblings associated with low maternal breast milk zinc concentration.

Symptomatic zinc deficiency developed in an exclusively breast-fed, full-term infant. Her older brother had also developed zinc deficiency while being exclusively breast-fed. Breast milk zinc concentrations were low throughout lactation, and this inadequacy is the likely cause of the deficiency in both infants.