Lennart Emtestam

Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity

Background  Hidradenitis suppurativa (HS) is a long‐standing disease with abscess and often fistula formation, predominantly in the axillae and groins. The disease is difficult to treat and has a severe impact on quality of life. A clinically relevant system for scoring disease severity is lacking in HS.

What causes hidradenitis suppurativa

Abstract:  Hidradenitis suppurativa (HS) – a rather common, very chronic and debilitating inflammatory skin appendage disorder with a notoriously underestimated burden of disease – has long been a playground for the high priests of nomenclature: Ask a bunch of eminent dermatologists and skin pathologists to publicly share their thoughts on what causes HS, and they will soon get entrenched in a heated debate on whether this historical term is a despicable misnomer. Fortunately, the recently founded Hidradenitis Suppurativa Foundation (HSF; http://www.hs‐foundation.org), to which EXP DERMATOL serves as home journal, has broken with this unproductive tradition and has encouraged publication of the current CONTROVERSIES feature. This is exclusively devoted to discussing the pathobiology of this chronic neutrophilic folliculitis of unknown origin. Although traces of terminological bickering remain visible, it does the HS experts in our virtual debate room credit that they engage in a constructive and comprehensive dissection of potential pathogenesis pathways that may culminate in the clinical picture we know under the competing terms HS or acne inversa. These experts sketch more often complementary than mutually exclusive pathogenesis scenarios, and the outlines of a conceivable consensus on the many open pathobiology questions begin to emerge in these CONTROVERSIES. Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy.

Increased nerve growth factor and its receptors in atopic dermatitis : an immunohistochemical study

Evidence suggests that neurotrophins may regulate certain immune functions and inflammation. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored using immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in early lesions of atopic dermatitis (AD). In AD involved skin, strong NGF-immunoreactive (IR) cells were observed in the epidermis. In some cases, a huge number of infiltrating cells with stronger NGF immunoreactivity was seen mainly in the dermal papillae. Some trkA immunoreactivity was observed in the outer membrane of cells in the basal and spinal layers of the epidermis. In the papillary dermis, a larger number of cells demonstrated strong trkA immunoreactivity. The p75 NGFr-IR nerve fibre profiles were increased (900 per mm2; p<0.001) compared to normal [the involved skin also differed from the uninvolved skin (p<0.05)] in the dermal papillae. These nerve fibres were larger, coarser and branched, some of them terminated at p75 NGFr-IR basal cells, and also revealed a stronger fluorescence staining than the controls or the uninvolved skin. In normal healthy volunteers and AD uninvolved skin, the NGF immunoreactivity was weak in the basal layer of epidermis. Only a few trkA positive cells were seen in the basal layer of the epidermis and upper dermis. The IR epidermal basal cells revealed a striking patchy arrangement with strong p75 NGFr immunostaining in the peripheral part of the cells, and short and thick NGFr-IR nerve fibre profiles appeared as smooth endings scattered in the dermis including the cutaneous accessory organs. Using NGF and p75 NGFr double staining, both immunoreactivities showed a weak staining in the epidermis and dermis in normal and uninvolved skin. In the involved dermis of AD, the intensity of p75 NGFr-IR nerves was stronger in areas where there were also increased numbers of NGF-IR cells. These findings indicate that NGF and its receptors may contribute to the neurohyperplasia of AD.

Correlation of impedance response patterns to histological findings in irritant skin reactions induced by various surfactants

Summary We have explored the use of measurements of electrical impedance to discriminate between the effects of different irritant substances upon the skin, and have studied the relationships between impedance and histopathological change. Three compounds with different chemical profiles were tested on volunteers: sodium lauryl sulphate, benzalkonium chloride and nonanoic acid. The concentrations selected were such that each irritant produced responses of a similar order, as judged by visual scores. The magnitude and phase of electrical impedance were measured and, for comparison, also the transepidermal water loss. Four physically distinct aspects (indices) were devised from the impedance data, and the values obtained were statistically analysed. The three irritants produced different effects, giving distinctive impedance patterns. These were also found to be reflected by three different types of histopathological skin response. Our results suggest that the indices can be used to classify irritant contact reactions, which it is difficult or impossible to achieve by other non‐invasive techniques.

Increased nerve growth factor- and tyrosine kinase A-like immunoreactivities in prurigo nodularis skin – an exploration of the cause of neurohyperplasia

Abstract Neurotrophins and their receptors play an important role in cutaneous nerve development and reconstruction after injury. Recent developments indicate that this group of molecules not only exert a neurotrophic action, but are also involved in immune responses and inflammation. Prurigo nodularis is a skin disease characterized by neurohyperplasia and intense itch. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored by immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in the disease. In normal healthy volunteers and in uninvolved skin, NGF immunoreactivity was seldom seen in the basal layer of the epidermis or in the dermis. In prurigo nodularis skin, there was also very little NGF immunoreactivity in the epidermis. However, in the dermis, a huge number of cells showed an NGF-like immunoreactivity. In normal skin of healthy volunteers, only a weak staining for tyrosine kinase A (trkA) was seen in the epidermis, whereas in the dermis, there was no trkA staining seen at all. However, in the prurigo nodularis tissue, the hyperplastic nerves clearly showed trkA immunoreactivity, and it seemed that the staining was only present in the axons. By NGF and p75 NGF receptor double-labelling, both immunoreactivities showed weak staining in the epidermis and dermis of normal skin. However, in the dermis of prurigo nodularis, strong staining for both NGF and NGF receptor antibodies was seen. NGF receptor-immunoreactive nerves were more dense in areas where there were more NGF-immunoreactive cells. The results indicate that in prurigo nodularis skin, NGF is overexpressed, locally infiltrated inflammatory cells may be the source of this NGF, and NGF and its receptors may contribute to the neurohyperplasia of the disease.

Electrical impedance measured to five skin depths in mild irritant dermatitis induced by sodium lauryl sulphate

The non‐invasive electrical impedance technique used in this study reflects structural changes in a tissue, and provides an estimate of the level of oedema by a simple impedance index.

Baseline electrical impedance measurements at various skin sites - related to age and sex.

During previous studies on the electrical impedance of the skin, we formulated a set of four physical indices that could be used to distinguish between the cutaneous effects produced by different chemical irritants. We now employ the electrical impedance technique to compare the properties of different anatomical areas of the skin, using the same set of indices.

Interobserver variability of clinical scores in hidradenitis suppurativa is low.

Background  Hidradenitis suppurativa (HS) is a chronic recurrent disease with scars and sinus tract formation that causes substantial impact on quality of life. For evaluation of HS and treatment results, a scoring system for disease severity (Hidradenitis Suppurativa Score, HSS) has been proposed.

Hidradenitis suppurativa: a common and burdensome, yet under-recognised, inflammatory skin disease

Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin condition that typically occurs after puberty. The primary clinical presentation is painful inflamed nodules or boils in the apocrine gland-bearing regions (armpits, genital area, groin, breasts and buttocks/anus) that progress to abscesses, sinus tracts and scarring. Severity is typically described according to three Hurley categories, with most patients having mild or moderate disease. Estimated prevalence is 1–4% worldwide and HS is three times more common in women than men. Patients’ disease burden includes intense pain, work disability and overall poor quality of life. Although the clinical signs of the disease can often be hidden by clothing, active HS is associated with a malodorous discharge that contributes to the disabling social stigma. Risk factors include smoking and obesity. Comorbidities include inflammatory bowel disease and spondyloarthropathies. The presentation of the disease is distinct, yet HS is not well-recognised except in dermatology clinics.

Expression pattern of somatostatin receptor subtypes 1–5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis

Abstract:  In psoriasis and atopic dermatitis, the inflammatory events have neurogenic components and the neuropeptides modify the functions of immuno‐active cells in the skin. Somatostatin is a neuropeptide with several neuroendocrine and immunomodulating properties and mediates its actions by five distinct subtypes of G‐protein‐coupled receptors (SSTR1‐5). This study describes the distribution of SSTR1–5, analysed with immunohistochemistry, in psoriasis, atopic dermatitis and controls. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. SSTR1–3 were strongly expressed in the epidermis of healthy skin, and in the skin of patients with psoriasis or atopic dermatitis. It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin. The intensity of the staining also varied considerably between the different layers of the epidermis, especially in psoriasis patients. In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1–4, but a weak expression of SSTR5. SSTR1–5 were strongly expressed in the sweat glands in all skin biopsies. Hair follicles and sebaceous glands expressed all five subtypes. Striated muscle fibres showed an intense positive expression of SSTR1–4, but a weak or negative expression of SSTR5. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin.