Geoffrey D. Cains

SAFETY AND EFFICACY OF MOMETASONE FUROATE CREAM IN THE TREATMENT OF STEROID RESPONSIVE DERMATOSES

The safety and efficacy of once daily application of mometasone furoate cream 0.1% was determined by comparison with twice daily applications of betamethasone dipropionate cream 0.05% in a single blind, dual centre, randomized study in patients with a variety of steroid‐responsive inflammatory dermatoses, the most common of which was psoriasis. Morning plasma cortisol levels revealed little adrenal suppression in either of the two study groups and there was no significant difference between the two groups. Routine laboratory investigations showed no trends in values outside the normal ranges that were of clinical significance. Less skin atrophy was seen in the group treated with mometasone furoate. In comparison to the betamethasone dipropionate treated group, those treated with mometasone furoate exhibited only slight evidence of skin atrophy, and this was not observed before four to twelve weeks of treatment. Eighteen percent of patients using mometasone reported adverse reactions but all were of limited duration and did not persist despite continued application of the drug. Nine percent of patients using betamethasone dipropionate reported adverse effects. Both drugs were found to be highly effective with no significant difference between the two groups at the termination of the treatment period. Of importance is the fact that whilst mometasone furoate is found to be a highly effective treatment for a variety of steroid‐responsive dermatoses, this drug has only a limited potential for production of local and systemic side effects. Thus, a high margin of safety can be expected for patients using this drug.

CLOFAZIMINE (LAMPRENE) IN THE TREATMENT OF DISCOID LUPUS ERYTHEMATOSUS

Clofazimine was administered, over a period of six months, in a dose of 100 mgm per day, to nine patients with discoid lupus erythematosus. There was complete suppression or improvement in every patient but this took up to three months to become evident. The main side effect was a pleasing suntan colour of the skin.

HALO ECZEMA AND JUNCTIONAL VAEVI: A CASE REPORT

Two separate instances of an acute eczematous reaction developing around a longstanding and previously quiescent pigmented naevus are described. From the evidence available this appears to be due to cell mediated immunological attack.

Systemic treatment of severe psoriasis

Severe psoriasis presents a difficult therapeutic challenge. Some modalities such as synthetic retinoids, phototherapy and methotrexate have been available for many years and need reappraisal, cyclosporin has only recently become available and requires careful administration. In this article we focus on the therapeutic modalities available to the dermatologist in Australia.

CHRONIC BULLOUS DISEASE OF CHILDHOOD—ASPECTS OF MANAGEMENT*

Five cases of chronic bullous disease of childhood are reported. The management of these cases is discussed and the use of sulphapyridine or dapsone in preference to oral corticosteroids is advocated.

Diagnosis by Frozen Section Examination, II: Results in Skin Lesions

A series of 910 frozen section examination of skin lesions is presented, and the results are analysed in detail and compared with others in the literature. The difficulties in histological diagnosis are discussed and contrasted with those of clinical diagnosis especially of pigmented lesions. SUMMARY In 910 consecutive frozen section examinations of skin lesions nine false positive reports were submitted, but only two were of major importance. False negative reports occurred with malignant melanomas when the lesion was small or heavily pigmented, and with other malignant lesions when the specimens were large (sampling error). Frozen section examination accurately identifies lesions that tend to be mistaken for malignant melanoma on clinical examination.

A systematic review and critical evaluation of reported pathogenic sequence variants in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a severe chronic inflammatory disorder characterized by recurrent painful deep‐seated nodules with a predilection to the apocrine‐bearing areas of skin. A minority of cases of HS are due to mutations in the γ‐secretase complex. Contention exists surrounding the pathogenicity of sequence variants and their effects upon Notch signalling. This systematic review was registered with PROSPERO (CRD42016041425) and was conducted in line with the PRISMA statement. Eligibility criteria for this review included published case reports, case series and reviews that identified sequence variants or protein or functional studies from patients with HS. Sixty‐two articles were identified reporting a total of 41 sequence variants – heterozygous missense (nine), splice site (nine), insertion resulting in frameshift (one), premature termination codon (19) and promoter region PSTPIP1 (three) – with 18 associated protein or functional studies. The American College of Medical Genetics and Genomics standards and guidelines on the interpretation of sequence variants were applied to each identified variant to assess evidence for pathogenicity. Twenty‐three variants were assessed as likely pathogenic, 17 of uncertain significance and one benign. The large number of variants of ‘uncertain significance’ is largely due to the variable number of functional studies. Four studies used Notch as a proxy for γ‐secretase function, with conclusions of nonpathogenicity based on the assumption of Notch signalling as the sole pathogenic process. The role of Notch‐independent signalling mechanisms requires further research. Limitations to this study include identification of variants of Mendelian inheritance and not complex polygenic traits.

Phenotypic heterogeneity implies heterogeneous pathogenic pathways in hidradenitis suppurativa

Summary of general pathogenic mechanisms Hidradenitis Suppurativa is a chronic inflammatory conditionmanifesting in recurrent painful deep-seated nodules and abscesseswith variable phenotypic presentations (1). Melnik and Plewig elo-quently describe the concept of HS as an autoinflammatory dis-ease with dysregulation of the gamma-secretase/Notch pathway(2); however, recent studies have identified ‘typical’ and ‘atypical’HS subtypes with differing morphology (nodules, comedones),lesion distribution (axillary, submammary and gluteal) and com-orbidity prevalence (1). The pathogenic hypothesis proposed byMelnik and Plewig (2) as well as reports of inconsistent responsesto systemic therapies (3,4) has led to suggestions that variablephenotypic presentations are suggestive of heterogeneous patho-genic inflammatory dysregulation within the gamma-secretase/Notch pathway paradigm (5). The complex interaction between metabolicsyndrome and HS Pascoe and Kimball describe the complex yet ‘established link’between metabolic syndrome and HS (6). Comorbidities includ-ing insulin resistance, glucose intolerance (7), dysregulated adipo-kine levels (8) (indirectly measured via BMI) (9) and bacterialsuperinfection (10) are all possible modulators of disease activity.These associations, however, have not taken into account the het-erogeneity of HS presentations and ensuing confounding relation-ships. The point prevalence of HS is quoted at 18% amongstbariatric surgery patients (11) with an odds ratio for metabolicsyndrome of 3.89 (95% CI 1.90–7.98) for a hospital HS cohort(12). However, analysis by Canoui-Poitrine et al. (1) shows statis-tically significant variation in BMI between ‘subtypes’ of HS, dis-crepancies which may confound existing results. Miller et al.(12), adjusting for BMI, revealed significant correlation betweendecreased HDL/elevated TG levels and HS in this cohort, suggest-ing an underlying metabolic disturbance independent of BMI.The role of adipose tissue as a dynamic endocrinological organacross all BMI ranges in HS requires further investigation (7).HS occurs in individuals with normal BMI (11), with 52.6% ofindividuals in Canoui-Poitrine’s analysis of BMI 25 or lower (1).The rates of metabolic derangements in this ‘atypical’ subtype areless well defined than their ‘typical’ counterparts. Hence, treat-ment focused on metabolic comorbidities may be appropriate in‘typical’ HS but their utility is as yet unclear in ‘atypical’ sub-types.

SAPHO syndrome associated with hidradenitis suppurativa and pyoderma gangrenosum successfully treated with adalimumab and methotrexate: a case report and review of the literature

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare inflammatory condition describing the combination of skin, bone, and joint manifestations that has a heterogeneous presentation. We report a case of severe SAPHO syndrome in association with hidradenitis suppurativa and pyoderma gangrenosum in a 27‐year‐old male. The patient had an initial migratory arthritis affecting the knees, ankles, metacarpophalangeal joints, proximal interphalangeal joints, wrists, shoulder, and lower back, which progressed to a persistent arthritis and swelling at the sternum, shoulders, wrists, hands, feet, and lower back. Radiographic changes were consistent with the diagnosis of SAPHO syndrome. Serum proinflammatory cytokine levels were significantly elevated and improved substantially after 3 months of therapy. Rationale for therapy in this patient was the observation that tumor necrosis alpha antagonists have been successfully used in SAPHO syndrome, and since arthropathy was so prominent in our patient, we elected to use adalimumab combined with methotrexate.

Adopting the orphan: The importance of recognising hidradenitis suppurativa as a systemic auto-inflammatory disease.

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