Frequency of undiagnosed psoriatic arthritis among psoriasis patients in Australian dermatology practice.

BACKGROUND: Psoriatic arthritis commonly develops in psoriasis patients and, if undiagnosed, can lead to potentially avoidable joint damage and an increased risk of comorbidity and mortality. Increased awareness of PsA symptoms among dermatologists provides an opportunity for earlier diagnosis, more timely therapy and prevention of disability. OBJECTIVE: To provide Australian epidemiological data on the frequency of undiagnosed PsA among psoriasis patients in dermatology practice, and to investigate the impact of psoriasis on quality of life and work productivity. METHODS: Nine tertiary centre dermatology practices enrolled patients presenting with plaque psoriasis and no prior rheumatologist-confirmed PsA diagnosis. Patients were screened using the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire and were referred to a rheumatologist for assessment of PsA status using CASPAR criteria if they had a PASE score ≥44. RESULTS: Based on the composite and sequential application of PASE and CASPAR criteria, undiagnosed PsA among psoriasis patients in this study is 9% [95% CI: 6, 12]. The PPV of PASE in this setting is 26% [95% CI: 19, 34]. Nail involvement and chronic large plaque psoriasis were identified as independent positive predictors of PsA, whereas scalp psoriasis was an independent negative predictor of PsA. Patients with moderate-to-severe psoriasis (PASI ≥15) had lower quality of life scores than patients with less severe psoriasis. CONCLUSION: In this study, the frequency of undiagnosed PsA in Australian dermatology practice was 9% among plaque psoriasis patients with no prior PsA diagnosis. Compared with psoriasis alone, the impact of undiagnosed PsA on health-related quality of life of psoriasis patients is substantial.

Porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) is a metabolic disorder of haem biosynthesis caused by decreased activity of uroporphyrinogen decarboxylase. Porphyria cutanea tarda is manifest by fragility, erosions, bullae, milia and scars on sun-exposed skin. Excess porphyrins in the skin interact with light of approximately 400 nm-wavelength radiant energy, forming reactive oxygen species. Porphyria cutanea tarda is categorized as familial, acquired or toxic. Factors that may induce clinical expression of PCT in susceptible individuals include alcohol, oestrogen, iron, polyhalogenated compounds and viral infections. Porphyria cutanea tarda is associated with an increased incidence of the haemochromatosis gene. Treatments for PCT include withdrawal of aggravating factors, phlebotomy and oral antimalarial medications.

Night blindness precipitated by isotretinoin in the setting of hypovitaminosis A.

A 16-year-old male developed night blindness 2 weeks after starting isotretinoin at a dose of 20 mg per day for cystic acne. He also had cystic fibrosis, complicated by hepatic cirrhosis. Despite long-term oral vitamin A supplementation, serum vitamin A levels were found to be 0.3 mumol/L (normal range 0.9-2.5 mumol/L). Oral vitamin A replacement was instituted with resolution of his visual symptoms in 6 months. Isotretinoin therapy was successfully continued with no deterioration in liver function. Isotretinoin has been reported to cause deterioration in night vision. In vitro evidence suggests isotretinoin may interfere with the processing of endogenous vitamin A in the retina. This case highlights the need for careful monitoring of serum vitamin A status in patients with malabsorptive states on isotretinoin therapy.

A case of spontaneous mutation in the keratin 9 gene associated with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma appears to be due to defects in keratin 9, the palmoplantar specific type 1 keratin. We report a case of spontaneous mutation, a C to T transition at codon 162, resulting in an arginine to tryptophan substitution in the 1 A region of the alpha helical rod domain of keratin 9. This provides further evidence that this codon is an important spot for mutation in keratin 9.

Grades of severity and the validation of an atopic dermatitis assessment measure (ADAM).

There has generally been a dearth of good clinical descriptions of grades of disease severity. The aim of this study was to produce reliable and valid descriptions of grades of severity of Atopic Dermatitis (AD). The ADAM (AD Assessment Measure) measure was used to assess AD severity in 171 male and female paediatric patients (mean age = 54 months) at the Royal Children's Hospital in Melbourne, Australia. The assessments were subject to Partial Credit analyses to produce clinically relevant "word pictures" of grades of severity of AD. Patterns of AD were shown to vary according to age, sex and severity. These descriptions will be useful for clinical training and research. Moreover, the approach to validation adopted here has important implications for the future of measurement in medicine.

Auricular ossification.

A patient with extensive bilateral auricular ossification presented with chondrodermatitis nodularis helicis on one side. The condition was otherwise asymptomatic. Ossification was detected on radiological and histological examination. Underlying medical conditions were not found. We believe this developed as a consequence of cold injury. Auricular ossification is an unusual cause of the so-called petrified external ear, in which the subcutaneous tissue is stony hard. It is more commonly caused by dystrophic calcification. Calcification and ossification are clinically identical and histological examination is required to definitively differentiate them.

Epidermolysis bullosa acquisita in childhood.

This case report of an 11-year-old girl describes a juvenile form of epidermolysis bullosa acquisita, an autoimmune disease of IgG antibodies to basement membrane type 7 collagen. Our case illustrates an unusually severe, acute inflammatory presentation of this condition with prominent mucosal and constitutional features requiring admission to a paediatric burns unit. The treatment consisted of supportive topical and systemic agents, prednisolone and dapsone. She responded to dapsone alone and the course of the illness was uneventful.

Atopic eczema: its impact on the family and financial cost.

OBJECTIVE: To evaluate the impact of childhood atopic eczema on families and assess the personal financial cost of its management. DESIGN: Cross sectional survey. SETTING: Paediatric dermatology and paediatric diabetology outpatient clinics. PATIENTS: Parents of 48 randomly selected children with atopic eczema and 46 with insulin dependent diabetes mellitus. MAIN OUTCOME MEASURES: The impact on family score, the reported cost of relevant medical treatments, medical consultations, relevant hospitalisation, and income loss. RESULTS: Families of children with moderate or severe atopic eczema had a significantly higher impact on family score than families of diabetic children. A conservative estimate of the annual personal financial cost of managing mild, moderate, and severe eczema was Aus$330, 818, and 1255, respectively. The financial cost to the community for the management of atopic eczema in the study groups was greater. The personal financial cost of managing eczema was greater than for asthma. CONCLUSION: Childhood atopic eczema has a profound impact on the social, personal, emotional, and financial perspectives of families.

House dust mite immunotherapy results in a decrease in Der p 2-specific IFN-gamma and IL-4 expression by circulating T lymphocytes.

BACKGROUND: Allergen-specific immunotherapy (IT) can be an important adjunctive therapy in the treatment of allergic disorders. Although it has now been used for over 80 yr, the precise mechanism of action remains unclear. Recently a number of studies have shown that cytokine production may be modified by IT, but different protocols have been used and different results obtained. OBJECTIVES: The aims of the present study were: (1) to document the allergen-specific expression of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) by peripheral blood cells in both untreated house dust mite (HDM) allergic patients (non-IT) and following at least 10 months of HDM-specific IT (post-IT); and (2) to determine whether alterations in these critical regulatory cytokines correlated with the clinical outcome of IT. METHODS: IT was undertaken with nine fortnightly subcutaneous injections of increasing amounts of a Dermatophagoides pteronyssinus (Dpt) extract, reaching a final dose of 10,000 PNU. This was followed by 6- to 8-monthly maintenance injections of 5000 PNU. For cytokine measurement, mononuclear cells were separated from peripheral blood and stimulated with the major Dpt allergen, Der p 2, for 18 h, after which mRNA was isolated and IL-4 and IFN-gamma cDNA were amplified by polymerase chain reaction (PCR). The presence of the particular cytokine was determined by visualization following electrophoresis on an agarose gel. The study was observational in nature being open and without a placebo group. RESULTS: Fifteen Dpt-sensitive patients who had not received HDM IT (non-IT), and 16 who had, were studied. In the non-IT group, 80% expressed IL-4 and 75% expressed IFN-gamma. In those post-IT, only 12.5% expressed IL-4 and 19% IFN-gamma. The two patients still expressing IL-4 post-IT had had very little clinical response. Six patients were studied both pre- and post-IT. Prior to IT, three were positive for both cytokines, two positive for IL-4 alone and one for IFN-gamma. Post-IT, all six were negative for IL-4 and five were negative for IFN-gamma. CONCLUSION: Allergen-specific IT results in a reduction in expression of the critical cytokines IL-4 and IFN-gamma in circulating lymphocytes. It is possible that this is a contributary mechanism in the beneficial effect of IT.

Fixed drug eruption to tartrazine.

An 11-year-old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights fire need to consider artificial flavours, colours and preservatives as potential culprits in classic drug eruptions.

Dermatophagoides pteronyssinus II-induced interleukin-4 and interferon-gamma expression by freshly isolated lymphocytes of atopic individuals.

Cytokines are known to play a major role in mediating many of the immunological and pathological features of allergic disease. Much of our understanding of cytokine production in response to allergens has come from studying allergen-specific T cell clones following long-term in vitro culture. This has largely been due to the lack of sufficiently sensitive assays to measure allergen-induced cytokine production by freshly isolated peripheral blood mononuclear cells (PBMCs). Here we have used the polymerase chain reaction to amplify reverse transcribed interleukin-4 (IL-4) and IFN gamma mRNA expressed by allergen-stimulated PBMCs from a variety atopic individuals. Using Der p II, a major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus, we have demonstrated that cells from HDM-sensitive atopic patients (n = 12), can be induced to express either IL-4 alone (three patients), IL-4 and IFN gamma (six patients), IFN gamma alone (two patients) or neither cytokine (one patient). Cells from 13 non-atopic control individuals were also stimulated with Der p II and cytokine mRNA production was studied. None expressed IL-4, while seven of 13 transcribed IFN gamma. Our results suggest that atopic individuals have allergen-reactive T cells at various stages of differentiation, with respect to the cytokines they produce. The use of this technique will aid in the further understanding of specific cellular hypersensitivity in allergic disease.

IL-4 production is increased in cigarette smokers.

Cigarette smoking has been associated with both increases in serum levels of total IgE and an increased risk of developing allergic-like symptoms. IL-4 and interferon-gamma (IFN-gamma) have reciprocal roles in the regulation of IgE synthesis, and as such prompted us to evaluate, in smokers, the production of these two cytokines. We demonstrate that phytohaemagglutinin (PHA)-induced IL-4 production by peripheral blood mononuclear cells (PBMC) of smokers (n = 19) is significantly higher than that of non-smokers (n = 10, P < 0.005). In addition, PBMC from heavy smokers, defined by the number of cigarettes smoked per day, produced significantly higher levels of IL-4 than those of light smokers. No difference between the groups was found for IFN-gamma production. Our data suggest an imbalance in cytokine production occurring in individuals who smoke. This imbalance, favouring IL-4 production, may be part of the mechanism responsible for the observed increases in serum IgE and allergic-like symptoms associated with cigarette smoking.

Interferon-gamma production in atopic dermatitis: a role for prostaglandins?

Peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) have a reduced capacity to produce interferon-gamma (IFN-gamma) in vitro, in response to phytohaemagglutinin (PHA) when compared to healthy non-atopic controls. This defect appears to correlate closely with the severity of AD at the time of sampling, with less IFN-gamma being produced by cells from patients with more severe disease. Enhanced production of IFN-gamma was observed as the patients clinical symptoms improved. In addition, IFN-gamma production could be increased by either pre-culturing the cells for 3 days prior to PHA stimulation or by addition of indomethacin to the culture medium. These observations suggest that the mechanism of reduced IFN-gamma production in AD is unlikely to be due to an intrinsic cellular defect. The possibility that prostaglandins mediate the suppressed production of IFN-gamma in AD was supported by demonstrating that exogenous prostaglandin E2 (PGE2) inhibited IFN-gamma production in PHA-stimulated PBMC. PGE2 at a physiological concentration (10(-9) M) was also shown to enhance interleukin 4 induction of IgE synthesis by PBMC cultures. Our data suggest that alterations in prostaglandin metabolism play a crucial role in the pathogenesis of AD by inhibiting the production of IFN-gamma.

Extracorporeal photochemotherapy in the treatment of cutaneous T-cell lymphoma. Complexity of objective evaluation.

The term cutaneous T-cell lymphoma (CTCL) encompasses the spectrum of diseases characterized by a monoclonal proliferation of malignant T lymphocytes predominantly of the mature T-helper cell type. These include mycosis fungoides, which is usually localized to the skin for many years, and the Sezary syndrome, the leukemic variant in which characteristic, bizarre lymphatic cells with deeply indented or cerebriform nuclei, the Sezary cells, infiltrate lymph glands and internal organs such as the spleen, liver, lungs, heart, and bone marrow. The condition is more common in men after their fourth decade. The treatment of CTCL varies depending on the stage of the disease. The skin of the patient is the primary index of effectiveness of therapy. Options range from topical steroids, topical nitrogen mustard, X-irradiation, electron beam irradiation, and 8-methoxypsoralen (8-MOP) combined with ultraviolet A photochemotherapy (PUVA), to leukapheresis and systemic chemotherapy. More recently, extracorporeal photochemotherapy (ECPC) has been introduced. The safety and efficacy of this modality is further investigated in six patients who fulfilled the criteria of diagnosis of CTCL. The problems encountered in objectively evaluating the clinical responses in the patients are outlined and improvements in the protocol to overcome these are suggested. The proposed mechanism of action is an immunostimulatory one and a procedure that is relatively free from side effects; it offers promise as a potential treatment for a difficult cancer.

Recombinant interferon-gamma inhibits the expression of IL-4 receptors on human lymphocytes.

Interferon gamma (IFN-gamma) has been shown to inhibit many of the activities of IL-4, including the induction of IgE synthesis and the proliferation of T cell clones. Here we demonstrate that IFN-gamma is able to inhibit the expression of IL-4 receptors on peripheral blood lymphocytes from both normal healthy donors and from patients with chronic lymphocytic leukaemia. Inhibition was shown to be dose-dependent and did not affect the binding affinity of the receptor as shown by Scatchard analysis. IFN-gamma was unable to displace labelled IL-4 from its membrane receptor, which demonstrates that IFN-gamma and IL-4 do not compete for the same membrane binding protein. The ability of IFN-gamma to down-regulate IL-4 receptors may be important in controlling certain immune responses.

Monosodium glutamate-related orofacial granulomatosis. Review and case report.

A case is reported in a 15-year-old white girl who had a swollen lower face and lips; a diagnosis of orofacial granulomatosis was made. It was suspected that her condition had an allergic basis because an increase in clinical signs and symptoms was shown to be related to the food additive monosodium glutamate. Treatment with a restricted diet resulted in resolution of the facial swelling.