Altered innate and adaptive immune responses in patients with hidradenitis suppurativa.
ABSTRACT The clinical improvement of hidradenitis suppurativa reported in a small number of patients with antitumour necrosis factor (anti-TNF)-alpha therapies supports the hypothesis for an altered immune response in these patients.
To evaluate the state of the innate and adaptive immune responses in patients with hidradenitis suppurativa.
Fifty-three patients and six healthy controls were studied. Blood was sampled and subpopulations of lymphocytes were analysed by flow cytometry; monocytes were isolated and their function was evaluated from the concentrations of TNF-alpha and interleukin (IL)-6 in supernatants of cell cultures after triggering with endotoxins (lipopolysaccharides). TNF-alpha and IL-6 were estimated by an enzyme immunoassay.
CD3/CD8 lymphocytes were lower in patients with involvement of the perineum than in controls; patients with involvement of the breast had higher levels of natural killer (NK) cells than controls. A negative correlation was found between years lapsing since initial presentation of lesions of hidradenitis and the percentage of NK cells. Monocytes isolated from healthy volunteers were more active for the secretion of TNF-alpha and IL-6 than those of patients with hidradenitis suppurativa.
A reduction in the percentage of NK cells over time and a lower monocyte response to triggering by bacterial components is observed in patients with hidradenitis suppurativa. Further research is needed to clarify if these changes are connected to an autoimmune mechanism in the pathogenesis of hidradenitis suppurativa.
Article: Hidradenitis suppurativa: a review.[show abstract] [hide abstract]
ABSTRACT: Hidradenitis suppurativa is a recurrent disease involving apocrine-bearing skin with a predilection for intertriginous areas, including genital skin. It has a highly variable clinical course. Mild cases may present as recurrent isolated nodules, while severe instances of the disease with chronic inflammation may lead to scarring, functional impairment, and rarely, squamous cell carcinoma. While genetic factors, patient characteristics, hormones and infection play a role in disease expression, a comprehensive understanding of the pathogenesis remains to be elicited. Additionally, effective treatment is largely unknown. While the mainstay of therapy had been surgery, and topical or systemic antimicrobial agents, other therapeutic modalities such as retinoids, hormonal therapy and immunosuppresive medications may also hold some promise.Dermatologic Therapy 02/2004; 17(1):50-4. · 1.96 Impact Factor
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ABSTRACT: Hidradenitis suppurativa (HS) is a chronic suppurative condition which is poorly responsive to treatment and is characterized by significant morbidity. Successful treatment of HS in patients treated with infliximab for concomitant Crohn's disease has been reported. More recent reports of positive responses to infliximab [an antitumour necrosis factor (TNF)-alpha agent] in patients who have HS but not Crohn's disease are encouraging. TNF-alpha is implicated in many inflammatory disorders and we wished to determine the efficacy of subcutaneous etanercept, a competitive inhibitor of TNF-alpha in the control of HS symptoms. We commenced six patients with severe, recalcitrant HS on etanercept (25 mg subcutaneously twice weekly in all cases). All patients had a normal chest X-ray and negative purified protein derivative test prior to treatment and were closely monitored throughout the treatment period for signs of infection. Patients self-assessed their disease activity and completed Dermatology Life Quality Index (DLQI) questionnaires immediately before the introduction of therapy and 24 weeks later in the case of four patients, and 12 weeks later in the case of two others. All patients were asked to estimate the time lapse between commencement of treatment and initial response. Treatment was well tolerated by all patients with no reported adverse reactions. A marked reduction in self-reported disease activity (mean reduction of 61% at 24 weeks), in DLQI scores (mean reduction of 64% at 24 weeks) and in relapse rates occurred. All patients rated etanercept as their most effective treatment to date. Our results show the effectiveness of etanercept in this group of patients with particularly challenging disease. Etanercept, unlike infliximab, may be administered subcutaneously, rendering costly day-case admissions unnecessary.British Journal of Dermatology 05/2006; 154(4):726-9. · 3.76 Impact Factor
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ABSTRACT: Host-defence defects in hidradenitis suppurativa patients have been suspected, but not proven. Activated neutrophils can destroy the surrounding tissues by a release of reactive oxygen species and active proteases. Peripheral neutrophils from 15 female patients (mean age 46, range 27-57 years) in an inactive state of their hidradenitis suppurativa, were studied and compared with 15 age-matched healthy female controls. There were no significant differences between patients and controls in the assessments of intracellular elastase activity, total content of antigenic elastase or release of elastase. Furthermore, no differences were found in total content and membrane expression of the receptors measured. The generation of free oxygen radicals, after stimulation with the protein kinase C activator phorbol myristate acetate, was significantly higher in the patients than in the controls, while there was no difference after Fc-receptor-mediated stimulation. Dysfunctional neutrophils might be involved in the pathogenesis of hidradenitis suppurativa, but the findings should be interpreted with caution because of the small number of observed cases.Acta Dermato Venereologica 06/2001; 81(2):96-9. · 3.49 Impact Factor