Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

Invasive dermatophyte infection with Trichophyton interdigitale is associated with prurigo-induced pseudoperforation and a signal transducer and activator of transcription 3 mutation.

Invasive dermatophyte infection, with extension beyond the dermis, in immunocompetent hosts is exceptionally rare. Dermatophytes are keratinophilic and are usually confined to the stratum corneum, hair and nails. Susceptibility to dermatophyte infections is incompletely understood, but inherited mutations in key signalling pathways of the innate immune system have been identified. We report the first case of an invasive dermatophyte infection associated with abrupt onset of a prurigo-induced pseudoperforation and a loss-of-function mutation in signal transducer and activator of transcription 3 (STAT3).

An exploratory study using framework analysis to investigate health-seeking behaviour in patients with psoriasis.

BACKGROUND: Psoriasis is a long-term inflammatory skin disorder, with negative effects on employment, relationships and social function, frequently causing reduced quality of life. People with psoriasis often present to secondary care late into their condition but the reasons for this are unknown. OBJECTIVES: To examine the patient pathway, health-seeking behaviour and drivers for referral to secondary care in patients with psoriasis. METHODS: Sixteen patients with mild-to-severe psoriasis, newly referred to secondary care participated in a semi-structured interview. Scripts were analysed by a thematic framework. RESULTS: The median duration of time living with psoriasis was 15 years at referral. Drivers of secondary care referral included rapid deterioration or extremis, development of comorbidities, knowledge of treatment options, and influence of partners and friends. Reasons for late presentation to secondary care include familial experience of psoriasis, lack of follow-up after the initiation of treatments, beliefs that psoriasis is incurable and must be tolerated, and that psoriasis is not life threatening and therefore not worthy of medical help and difficulty in obtaining a secondary care referral. A common pathway from seeking help at psoriasis onset, evolving into the development of delayed health seeking later in the pathway, was identified. CONCLUSIONS: Identifying the causes of delay in presentation to secondary care and effective treatment ascertains key areas to target. Health seeking early in the disease pathway provides a 'window of opportunity' for intervention, which may enable people with psoriasis to obtain early, effective treatment and achieve their full life potential.

Nutritional issues in patients with severe neutropenia.

OBJECTIVES: To provide information on the assessment and management of the nutritional needs of patients with severe neutropenia. DATA SOURCES: Textbook chapters, research articles, and review articles. CONCLUSIONS: Malnutrition is a common result of high-dose chemotherapy treatment. Clinical outcomes are directly related to careful assessment, early intervention, and ongoing evaluation and monitoring in the severely neutropenic population. IMPLICATIONS FOR NURSING PRACTICE: Early assessment, management, and psychological support are essential in meeting the needs of this patient population.

A study of referral patterns among Queensland general medical practitioners to chiropractors, osteopaths, physiotherapists and others.

BACKGROUND: In Queensland, Australia, patients with work-related injuries must receive a referral from a general medical practitioner to receive treatment from such "nontraditional" practitioners as physiotherapists, chiropractors or osteopaths, even though these nontraditional practitioners are primary care providers outside of the workers' compensation system. The Chiropractors' Association of Australia (Queensland Branch) (CAAQ) believed that injured workers wishing to receive chiropractic care stood little chance of obtaining a medical referral. On the other hand, the General Manager of the Workers' Compensation Board of Queensland maintained that injured workers had little difficulty obtaining such a referral for chiropractic care. OBJECTIVE: To canvass general medical practitioner attitudes and referral patterns to chiropractors, osteopaths, physiotherapists and other nontraditional practitioners (naturopaths). DESIGN: A descriptive study in which 1509 general medical practitioners in private practice in Queensland were invited to respond to a mailed questionnaire. The sample represented 50% of all such practitioners in Queensland. RESULTS: A 52% response rate was obtained with 784 (638 male, 142 female general practitioners) questionnaires returned. Respondents' ages ranged from 27 to 79 yr. The respondents' years in practice ranged from 1 to 55 yr. The survey showed that attitudes and referral patterns were distinctly different depending on the nontraditional practitioner group in question. CONCLUSION: The survey results confirm that general medical practitioners are highly unlikely to have professional dealings with chiropractors and osteopaths, including referral of patients to said providers, even if the patient requests such a referral, and that general medical practitioners are much more likely to have professional dealings with physiotherapists than with any of the other nontraditional groups considered.

Allogeneic peripheral blood stem cell transplant for myelodysplasia after chemotherapy for post-transplant lymphoma in a cardiac transplant recipient at 10 years.

A 32-year-old male received an allogeneic peripheral blood stem cell transplant (alloPBSCT) for myelodysplasia from his one HLA-A antigen mismatched brother. He is alive with trilineage engraftment and without active GVHD 200 days after transplant. In July 1986 he underwent orthotopic cardiac transplantation for viral cardiomyopathy and has received continuous immunosuppressive therapy. A post-transplant lymphoproliferative disorder with Hodgkin-like histopathology was diagnosed in August 1993 and was successfully treated with four cycles of MOPP chemotherapy. Due to persistent pancytopenia he underwent a bone marrow aspiration and biopsy in May 1996 which revealed monosomy 7 and morphologic changes compatible with myelodysplasia. This is the first report of a cardiac transplant recipient receiving an allogeneic hematopoietic stem cell transplant.

Effects on pulmonary function of two regimens of chemotherapy for AIDS related Kaposi's sarcoma.

We retrospectively analysed serial pulmonary function tests in 14 HIV infected patients receiving either bleomycin and vincristine or liposomal doxorubicin therapy (Doxil) for AIDS related Kaposi's sarcoma. There was a significant reduction in the carbon monoxide transfer coefficient in bleomycin treated patients compared with patients treated with Doxil. No other significant changes in pulmonary function, including the carbon monoxide diffusing capacity, were observed. These preliminary findings suggest that HIV infected patients with Kaposi's sarcoma, who are receiving bleomycin, may be at risk of accelerated pulmonary dysfunction. A larger prospective study should be performed to enable further investigation.

Liposomal doxorubicin for treatment of AIDS-related Kaposi's sarcoma.

Sixteen patients with advanced AIDS-related Kaposi's sarcoma received liposomal doxorubicin (Doxil, Liposome Technology, Menlo Park, California) at 20 mg/m2 every 2 or 3 weeks in an open label study, and were evaluated for efficacy and toxicity. Eleven patients achieved a partial remission and five had stable disease. The median time to achieve a maximum response was two cycles (range 1-3) and the median duration of response was 14 weeks (range 6-30). Myelosuppression was the commonest adverse event; one patient was withdrawn because of neutropenia. Other adverse events were uncommon and mild. Liposomal doxorubicin is an effective and safe single agent treatment for advanced AIDs-related Kaposi's sarcoma.

Five case reports of high grade non-Hodgkin's lymphoma in human immunodeficiency virus-1 negative homosexual men.

High grade non-Hodgkin's lymphoma accounts for only 5%-10% of all non-Hodgkin's lymphoma. Infection with the human immunodeficiency virus increases the risk of developing high grade, usually B-cell, lymphoma, which has been noted to occur more commonly in homosexual men. These lymphomas often have unusual clinical presentations. We report five cases of high grade non-Hodgkin's lymphoma in HIV negative homosexual men who presented to our hospital in a 13-month period. As a major centre for the treatment of the acquired immune deficiency syndrome, there may be a self-selected homosexual population attending for medical care, and thus a bias in the relative incidence of lymphoma seen in this group.

Comparison of stationary vs ambulatory 24-hour pH monitoring recording systems.

Twenty-four-hour pH monitoring of the esophagus is frequently performed to assess gastroesophageal reflux. We performed a prospective study to determine if results obtained from stationary and ambulatory pH recording systems are comparable. Two groups of patients were studied. Group I consisted of 12 patients monitored simultaneously by both a stationary and an ambulatory pH recording system, each system having a separate pH and reference electrode. In group II, in order to eliminate electrode variability, 10 patients were monitored simultaneously with both systems and a common single pH and reference electrode. In group I, significant correlations were found in six reflux parameters measured and in the 24-hr composite score (r greater than or equal to 0.8722). However, in three of the 12 patients, marked discrepancies were noted in the composite score calculated by the stationary and ambulatory recording systems. Small variations in the pH level recorded by different pH electrodes may have accounted for the discrepancies. In group II, where electrode variability was eliminated, a better correlation was noted between all parameters measured (r greater than or equal to 0.991), and no discrepancies were noted between calculated composite scores. We concluded that the stationary and ambulatory recording systems tested are comparable in measuring 24-hr esophageal pH.