Dunja Ana Vekic

Staphylococcus lugdunensis: case report and discussion

Staphylococcus lugdunensis has been reported as a highly virulent coagulase-negative staphylococcus (CoNS) species implicated in endocarditis and joint infections. Recent studies have confirmed that S. lugdunensis is a significant pathogen in causing skin and soft tissue infections, with a clinical incidence that is likely to be underreported. A 59-year-old HIV-positive man presented with an erythematous lesion measuring 2 × 3 cm on his lower back with a central punctum, (Fig. 1). The surrounding skin was tender to palpation with mild erythema and induration. There was no associated fever or any history of recent injury, procedure or trauma. His CD4 count was > 800 and the HIV viral load was undetectable, with a nadir CD4 count of 380 in 1996. The lesion was drained and the seropurulent fluid sent for culture and microscopy, with S. aureus as the suspected pathogen documented on the pathology request form. Results showed leucocytes 3+, with no bacteria visualised on microscopy. Culture sensitivities demonstrated a pure growth of a CoNS, with subsequent laboratory-initiated speciation performed in the light of pure growth enabling the identification of S. lugdunensis. Antibiotic susceptibilities demonstrated the organism to be susceptible to all antibiotics tested, including penicillin. Following drainage and commencement of oral flucloxacillin the lesion reduced in size, with complete resolution observed within 4 weeks. Multiple similar lesions were excised over a 7-year period, prior to and following the patient’s presentation; however histopathology confirmed these to be epidermoid cysts and cultures were not performed.

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.

1. Herbst RA, Uter W, Pirker C et al. Allergic and non-allergic periorbital dermatitis: patch test results of the Information Network of the Departments of Dermatology during a 5-year period. Contact Dermatitis 2004; 51: 13–19. 2. Feser A, Plaza T, Vogelgsang L et al. Periorbital dermatitis – a recalcitrant disease: causes and differential diagnoses. Br. J. Dermatol. 2008; 159: 858–63. 3. Landeck L, John SM, Geier J. Topical ophthalmic agents as allergens in periorbital dermatitis. Br. J. Ophthalmol. 2014; 98: 259–62. 4. Kligman AM. Lanolin allergy: crisis or comedy. Contact Dermatitis 1983; 9: 99–107. 5. Ellis FA. Allergic contact dermatitis due to wool fat and cholesterol. Arch. Derm. Syphilol. 1947; 56: 801–6. 6. Eiermann HJ, Larsen W, Maibach HI et al. Prospective study of cosmetic reactions: 1977–1980. North American Contact Dermatitis Group. J. Am. Acad. Dermatol. 1982; 6: 909–17. 7. Landeck L, John SM, Geier J. Periorbital dermatitis in 4779 patients – patch test results during a 10-year period. Contact Dermatitis 2014; 70: 205–12. 8. Rietschel RL, Warshaw EM, Sasseville D et al. Common contact allergens associated with eyelid dermatitis: data from the North American Contact Dermatitis Group 2003–2004 study period. Dermatitis 2007; 18: 78–81. 9. Corazza M, Masieri LT, Virgili A. Doubtful value of patch testing for suspected contact allergy to ophthalmic products. Acta Derm. Venereol. 2005; 85: 70–1.

Drug-associated hidradenitis suppurativa: A systematic review of case reports

2. Gooderham M, Papp K. The psychosocial impact of hidradenitis suppurativa. J Am Acad Dermatol. 2015;73(5 suppl 1): S19-22. 3. Tiplady B, Jackson SH, Maskrey VM, Swift CG. Validity and sensitivity of visual analogue scales in young and older healthy subjects. Age Ageing. 1998;27:63-66. 4. Flytstr€ om I, Stenberg B, Svensson A, Bergbrant IM. Patients’ visual analog scale: a useful method of assessing psoriasis severity. Acta Derm Venereol. 2012;92:347-348. 5. Tavakol M, Dennick R. Making sense of Cronbach’s alpha. Int J Med Educ. 2011;27:53-55.

Hidradenitis suppurativa: A neglected disease in Indigenous Australians

We report the first case series of hidradenitis suppurativa in patients of Indigenous Australian heritage. The incidence and ethnicity of populations affected by this condition are not known. The high comorbid disease burden and socioeconomic disadvantage that is well recognised in the Indigenous Australian population poses significant challenges to therapeutic outcomes.

Hidradenitis suppurativa, a review of pathogenesis, associations and management. Part 1

Hidradenitis suppurativa is a chronic, painful, autoinflammatory condition resulting in nodules, abscesses and sinus tracts. We present an evidence‐based review providing new understanding of the pathogenesis of hidradenitis suppurativa and associated comorbidities. By the nature of their speciality, dermatologists are uniquely positioned to investigate and treat patients.

Pharmaceutical Benefits Scheme listing of adalimumab for hidradenitis suppurativa: Is hidradenitis suppurativa a life-changing drug or does lifestyle change the drug?

Hidradenitis suppurativa is a chronic inflammatory disease of intertriginous tissues manifesting as recurrent, painful nodules, abscesses, sinuses and scars with a profound physical and psychological impact. With an estimated prevalence of 0.03–4%, hidradenitis suppurativa is closely associated with the metabolic syndrome, androgen dysfunction and smoking. The clinical course and disease severity is variable, but a suboptimal response to traditional medical therapy is near universal. From 1 July 2017 the Australian Pharmaceutical Benefits Scheme has listed adalimumab (a fully human, monoclonal antibody inhibiting circulating tumour necrosis factor alpha) for moderate to severe hidradenitis suppurativa. This provides individuals living with hidradenitis suppurativa increased access to this affordable, potentially lifechanging therapy. The current Pharmaceutical Benefits Scheme criteria for adalimumab in hidradenitis suppurativa are listed in Table 1. Symptoms in a proportion of patients with hidradenitis suppurativa ameliorate when lifestyle factors such as ceasing smoking and weight loss therapy are addressed. However a significant minority have persistent severe and recalcitrant disease despite maximum lifestyle interventions, or are unsuccessful in addressing these factors. As these lifestyle issues are thought to contribute to inflammation in hidradenitis suppurativa, addressing them may have bearing on the efficacy of adalimumab. In other inflammatory diseases, no significant variations in the efficacy of adalimumab have been reported with regard to smoking status, bodyweight or diabetic status in Crohn disease, palmoplantar psoriasis or chronic plaque psoriasis. No similar studies have been undertaken in patients with hidradenitis suppurativa to date. Evidence exists in patients with psoriasis that smoking and diabetes predispose to an increased risk of serious infection (defined as a risk of death, permanent disability or prolonged hospitalisation) during treatment with adalimumab. Given the comparable association of both hidradenitis suppurativa and psoriasis with metabolic syndrome (hidradenitis suppurativa: OR 2.22; 95% CI 1.62– 3.06) and psoriasis (OR 2.14; 95% CI 1.84–2.48) it is prudent to assume that patients with hidradenitis suppurativa face a risk of infection. Indeed, hidradenitis suppurativa may have a stronger association with metabolic syndrome than psoriasis, particularly in light of the contribution of metabolic syndrome towards the inflammatory burden of the disease. This is exemplified by the reports of clinical improvement in patients with hidradenitis suppurativa with metformin and weight loss strategies including bariatric surgical intervention. Therefore, continuing to address lifestyle contributions to the activity of hidradenitis suppurativa, such as smoking, metabolic syndrome and weight loss (both before and during treatment with adalimumab) may have dual benefits. Firstly, it may help to minimise the risk of serious infection, and secondly, it may contribute to the ongoing control of inflammatory disease activity. Although current treatment guidelines and algorithms state that weight loss and smoking cessation should be discussed (if relevant) at every consultation, the data to support these recommendations is based upon data from other inflammatory disorders such as psoriasis and Crohn disease and may not be an accurate representation of the risk in hidradenitis suppurativa. The recent approval of adalimumab on the Pharmaceutical Benefits Scheme should be viewed as a triumph for patients with hidradenitis suppurativa. However, it is important for clinicians to recognise that until further evidence to the contrary emerges, the ongoing management of lifestyle contributions to hidradenitis suppurativa activity is still needed, even in the setting of effective adalimumab therapy.