A prospective trial of the effects of isotretinoin on quality of life and depressive symptoms.

BACKGROUND: Isotretinoin is an efficacious treatment for acne, but has been controversially linked with depression. OBJECTIVES: This study aimed to examine the effects of isotretinoin on quality of life(QoL) and depression using a prospective design. METHODS: The WHOQOL-BREF QoL measure and Centre for Epidemiological Studies Depression Scale were administered to consecutive outpatients with acne who were prescribed either isotretinoin (n = 65) or antibiotic treatment (n = 31).Patients and physicians rated acne severity independently. Groups were compared at baseline with a matched community sample (n = 94) and measurements repeated at 3 months for treatment groups. RESULTS: There were no differences between the three groups at baseline in terms of age, gender, depression or overall QoL. Acne was more severe in the treatment groups (P < 0·001). Depression was negatively correlated with QoL (P < 0·001)and hence was included as a covariate in repeated-measures analyses of QoL.Acne improved over time in both treatment groups (F = 48·2, P < 0·001). There was no detectable deterioration in depression score in either group (F = 1·1, not significant). QoL in the physical and social domains improved (P < 0·001) while psychological and environmental QoL was unchanged over time. The improvement in social QoL was greater in the isotretinoin group (P < 0·05). Those patients with higher baseline depression scores showed greater improvements in physical, psychological and social QoL (P < 0·001). CONCLUSIONS: Treatment of acne improves QoL, particularly in those with more depressive symptoms at the outset. Mood deterioration was not detected, but the possibility of subtle or rare mood effects of isotretinoin cannot be ruled out.

The effect of extracorporeal photopheresis on intracellular cytokine expression in chronic cutaneous graft-versus-host disease.

BACKGROUND: Cytokines derived from T helper (Th)1 lymphocytes are thought to be involved in the pathogenesis of graft-versus-host disease (GVHD) and extracorporeal photopheresis (ECP) has been reported to affect Th1/Th2 lymphocyte ratios. It may also influence the balance of cytotoxic Tcells (Tc1/Tc2). OBJECTIVES: This study was formulated to assess the effect of ECP on the cytokine profiles of peripheral blood (PB) lymphocytes from patients with chronic GVHD. PATIENTS AND METHODS: Nine patients were studied. Peripheral blood was sampled at baseline and between 3 and 4 months of therapy when clinical effects are demonstrable. Intracellular cytokine production was assessed in vitro by stimulating PB lymphocytes with phorbol-12-myristate 13-acetate (PMA), inhibiting cytokine release and staining with fluorescein-labelled monoclonal antibodies to interleukin (IL)-2, interferon gamma (IFN-gamma) and IL-4. Flow cytometry analysis gave the absolute number and the percentage of cells expressing a particular cytokine within each lymphocyte subset. RESULTS: Absolute counts of CD3, CD4, CD8, CD19 and CD16+ cells per microlitre were recorded before and after ECP. There was a small but non-significant reduction in all subsets after 3 months of ECP. The percentage of cells expressing IL-2 and IFN-gamma rose following ECP in both the CD4 and CD8 subsets. However, only the percentage of CD4 cells expressing IFN-gamma reached statistical significance (P = 0.02; 95% confidence interval, CI 0.6-15.6). There were no significant changes in the percentage of CD4 cells expressing IL-4. CONCLUSIONS: Our findings appear to be inconsistent with current theories regarding the pathogenesis of GVHD as increased production of Th1 or Tc1 cytokines might be expected to exacerbate GVHD. However, chronic GVHD is characterized by a relative deficiency of IL-2 and IFN-gamma producing cells compared with other patients post-bone marrow transplantation (BMT). This indicates that Th1 and Tc1 cytokines are depleted in chronic GVHD. Thus, by reducing disease activity, ECP could allow cytokine production by these cells to recover. This indicates that the therapeutic effect of ECP is mediated by a different mechanism, and that the changes observed in this study are epiphenomena.

Comparison of assessments of severity and quality of life in cutaneous disease.

Clinicians are, by profession, capable assessors of severity of disease. Whether from severity they can deduce a patient's Quality of Life (QoL) is debatable. This study compared scores for physician-assessed severity with the corresponding scores for patient QoL, as assessed using Dermatology Life Quality Index (DLQI) questionnaires in 57 dermatological out-patients. Although there was some degree of correlation between the two measures (r = 0.56), interpretation of QoL from disease severity is clinically unreliable. Thus a physician's assessment of QoL requires formal assessment using a tool such as the DLQI.

Photoallergic contact dermatitis is uncommon.

BACKGROUND: Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare. OBJECTIVES: To analyse the data from 2715 patients who underwent photopatch testing at St John's Institute of Dermatology during the period 1983-98. METHODS: A retrospective analysis of all positive photopatch test episodes was undertaken with the results retrieved from the environmental dermatology database and further verified with the original archived patch test documentation for each individual patient. RESULTS: In 111 patients with positive reactions (4.1%), there were 155 AC or PA reactions to allergens in the photopatch test series. Eighty PA reactions were observed in 62 (2.3%) patients (32 men and 30 women, age range 28-75 years), with UV filters accounting for 52 positive reactions (65%), drugs 16 (20%), musk ambrette 11 (14%) and the antiseptic trichlorocarbanilide one (1%). The most common UV filter photoallergen was benzophenone-3 with 14 positive results, followed by benzophenone-10 (n = 9), isopropyl dibenzoylmethane (n = 6), p-aminobenzoic acid (PABA) (n = 5), octyl dimethyl PABA (n = 5), butyl methoxydibenzoylmethane (n = 4), isoamyl methoxycinnamate (n = 2), ethyl methoxycinnamate (n = 2), octyl methoxycinnamate (n = 2), amyl dimethyl PABA (n = 2) and phenylbenzimidazole sulphonic acid (n = 1). A similar number of AC reactions to UV filters was detected in this study. Thus 49 patients (1.8%) had a total of 75 reactions: 51 due to UV filters and 24 as a result of exposure to fragrances and therapeutic agents. Benzophenone-10 accounted for 13 AC reactions and benzophenone-3 for eight reactions. Twenty-two patients had a PA reaction alone, whereas 19 patients had chronic actinic dermatitis and 15 patients polymorphic light eruption (PLE) in addition. Thus, 34 of the 62 patients (55%) had a preceding underlying photodermatosis. CONCLUSIONS: These results show a low yield of positive photopatch tests. Thus, despite the large increase in the use of UV filters over the last decade, the development of PA reactions remains rare. Furthermore, most of the common UV filter photoallergens identified in this study, including PABA, amyl dimethyl PABA and benzophenone-10, are now rarely used in sunscreen manufacture, while isopropyl dibenzoylmethane was voluntarily removed from the market in 1993. Currently, benzophenone-3 is the commonest contact photoallergen still in widespread use. In contrast, the UVB filter octyl methoxycinnamate, used in a number of sunscreens, produced only two positive PA reactions in 12 years of testing. Nevertheless, although these reactions are extremely rare, patients with photodermatoses such as PLE and chronic actinic dermatitis do represent a group of patients at increased risk of developing photoallergy. Further photopatch test series should be regularly reviewed and updated, as the relevance of individual photoallergens changes over time. Currently, there is no evidence that PA reactions represent a common clinical problem.

Erythema gyratum repens and acquired ichthyosis associated with transitional cell carcinoma of the kidney.

Both erythema gyratum repens (EGR) and acquired ichthyosis are distinctive dermatoses which have strong associations with internal malignancy. EGR usually precedes the diagnosis of malignancy whereas acquired ichthyosis commonly manifests after the detection of malignancy. We report a patient who initially presented with a figurate eruption of EGR which later developed into a widespread ichthyosis with disappearance of the serpiginous rash. Further investigations revealed an underlying transitional cell carcinoma of the kidney, an association which has not previously been reported with either EGR or acquired ichthyosis. The occurrence of two paraneoplastic skin disorders in the same patient may be explained by tumour cell secretion of transforming growth factor alpha, which has been shown to be mitogenic for keratinocytes.

Systemic B-cell lymphoma presenting as an isolated lesion on the ear.

We report a case of systemic B-cell lymphoma that presented as an isolated cutaneous lesion on the ear, mimicking a primary cutaneous B-cell lymphoma. Although there was no clinical evidence of systemic disease, bone marrow involvement was found on further investigation and subsequent immunoglobulin gene analysis revealed an identical clone in the skin lesion and bone marrow aspirate. Evidence of a t(14 : 18) translocation was not identified. This case is unusual for several reasons. First, involvement of the pinna as a presenting feature of systemic lymphoma has not been reported previously. Second, the cutaneous lesion had been present for 3 years prior to diagnosis and there has been no clinical progression of systemic lymphoma during 2 years of follow-up. Third, the lymphoma does not correspond exactly to any of the entities in the REAL classification of systemic B-cell lymphoma. This case underlines the indolent nature of some systemic B-cell lymphomas and the need to investigate thoroughly patients with disease apparently confined to the skin.

Persistent ulcerated necrobiosis lipoidica responding to treatment with cyclosporin.

We report two patients with severe ulcerated necrobiosis lipoidica (NL) who responded to cyclosporin. One patient had suffered persistent ulceration for a period of 7 years and the other had NL of recent onset. In both cases, ulceration healed completely after 4 months of therapy, and both patients have remained free of ulceration since discontinuing therapy. The possible mode of action of cyclosporin in the context of this debilitating disease is discussed.

Necrobiotic cutaneous T-cell lymphoma.

We report 3 patients with granulomatous cutaneous T-cell lymphoma (CTCL) who showed necrobiosis histologically with palisading granulomas. Although granulomatous change may be present in up to 4% of cases of CTCL, necrobiosis is rare. Misdiagnosis may occur if epidermotropism is minimal or if atypical cells are masked by the granulomatous infiltrate. T-cell receptor gene analysis confirmed the presence of clonal T-cell populations in lesional skin from all 3 cases.

Striae formation in two HIV-positive persons receiving protease inhibitors.

Steroidal side effects such as "buffalo hump" and visceral abdominal fat accumulation have been reported in association with protease inhibitors. We report two cases of severe disfiguring striae formation in patients with HIV who recently started indinavir therapy. These changes occurred within 3 months of starting treatment.

Isoniazid induced pellagra despite pyridoxine supplementation.

Although pellagra is a recognized complication of isoniazid therapy, the diagnosis may be overlooked or delayed--sometimes with life-threatening consequences. We report a case of isoniazid-induced pellagra which occurred despite pyridoxine supplementation. Drug withdrawal and supplementation with niacin led to a rapid and sustained clinical improvement. The possible mechanisms of isoniazid induced pellagra are discussed.

Staphylococcal scalded skin syndrome in an adult associated with methicillin-resistant Staphylococcus aureus.

We report the first adult case of staphylococcal scalded skin syndrome (SSSS) due to methicillin-resistant Staphylococcus aureus (MRSA). This case is particularly unusual as the MRSA produced toxic shock syndrome toxin 1 and enterotoxin, but not exfoliatoxin. SSSS was originally described in neonates and is thought to result from exfoliatins which produce subcorneal splitting of the epidermis and are only produced by certain strains of S. aureus. This case reflects the range of toxins that can be associated with SSSS and the clinical manifestations of MRSA infection in adult patients.

Livedoid vasculitis: a manifestation of the antiphospholipid syndrome?

Livedoid vasculitis, otherwise known as segmental hyalinizing vasculitis or livedo reticularis with summer ulceration, is a chronic disease with lesions affecting the feet and lower legs. Early lesions show petechiae, but characteristic features are recurrent, bizarrely shaped ulcers that heal to leave hyperpigmentation and atrophie blanche. The aetiology of the disorder is unknown, but the histology shows fibrin deposition within both the wall and lumen of affected vessels. The absence of a sufficient perivascular infiltrate or leucocytoclasia argues against a vasculitis, being more in keeping with a thrombo-occlusive process. Four patients with livedoid vasculitis with ulceration are described, all of whom had associated raised anticardiolipin antibodies but no other evidence of systemic disease. We suggest that livedoid vasculitis may be a manifestation of the antiphospholipid syndrome and recommend that all patients are screened for this. We also discuss treatment options for this often resistant condition.

Thalidomide-induced toxic pustuloderma.

We report a case of toxic pustuloderma secondary to thalidomide in a patient with severe nodular prurigo. To our knowledge this is the first reported case. With the increasing use of thalidomide for a variety of dermatological conditions it is clearly important that this rare side-effect now be recognised.