Self-management-competency as a new target in Hidradenitis suppurativa care.

Background: Hidradenitis suppurativa affects approximately 1% of the population.Objective: Highlighting the relevance of self-management-competency as a new therapeutic target.Method: 258 patients from the 'Epidemiology and Care in Acne inversa (EpiCAi)' project were included in the study. Disease burden was measured by patient-rated questionnaires in terms of disease activity, pain, quality of life, depression and insomnia and correlated with the domains of the health education impact questionnaire (heiQ) measuring self-management-competency.Results: 66 male (25.6%) and 192 female (74.4%) patients, with a mean age of 40.3 ± 10.24 years were included. Mean scores of pain on the numeric rating scale (NRS), Dermatology Life Quality Index (DLQI) and Hospital Anxiety and Depression Scale (HADS) were 5.11 ± 2.68, 11.35 ± 7.79 and 13.71 ± 7.57, respectively. The Insomnia severity index (ISI) showed a mean of 9.58 ± 5.76. The HADS has the highest increased total risk across all heiQ domains. With respect to the heiQ domains, the highest exposure can be attributed to improving constructive attitudes and approaches as well as decreasing emotional distress.Conclusion: There is a clear association of self-management-competency with overall disease burden, which underlines the need for psychoeducational support. This study provides ideas to develop new possible strategies of care.

[Topical and novel device-based therapies for mild hidradenitis suppurativa]. / Lokale und neue apparative Therapien der milden Hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin folds, which requires more outpatient treatment alternatives. Although the disease was previously treated using surgery, new treatment modalities now allow the effective treatment of mild and moderate cases in an ambulatory care setting. AIM OF STUDY: Local and instrument-based therapies are presented and their efficacy and safety profiles are highlighted. MATERIALS AND METHODS: Clinical evidence for each therapeutic modality are presented and current treatment developments are analyzed based on the future treatment of HS patients in Germany. RESULTS: Effective treatments for outpatient care of HS patients include topical clindamycin, resorcinol, and intralesional corticosteroids. New devices such as LAight therapy (combining intense pulsed light [IPL] with radiofrequency) are available, which can be used as monotherapy or adjunct therapy in combination with systemic treatment and/or surgery for the management of HS. CONCLUSION: Evidence-based use of local treatments can provide more efficient outpatient and self-administered strategies, which improves the quality of life of HS patients, especially for patients with recurrent mild and moderate disease.

[Need for real-world data studies on hidradenitis suppurativa/acne inversa treatment]. / Bedarf von Real-World-klinischen Therapiestudien für die Hidradenitis suppurativa/Acne inversa.

Publication of real world data on the results of treatment with (approved) drugs is important to allow for a reasonable judgement about the efficacy of a medication, especially since due to the nature of controlled clinical studies certain patient groups, who in daily clinical routine would best benefit from such new treatments, are excluded from study inclusions. In the present review, real-world data on the treatment of hidradenitis suppurativa (HS) are summarized. It appears that adalimumab, as the only approved biological treatment so far, represents a cost-efficient and effective therapy. Patient education is important to increase treatment adherence and efficacy. The baseline IHS4 score has proven to be a meaningful predictor for recurrences during adalimumab therapy. Additional publications on real-world data including high numbers of patients with different risk factors are required to meaningly evaluate the evolving therapeutic spectrum of treatment options for HS in clinical practice.

[What is a granuloma?] / Was ist ein Granulom?

The histogenesis of granulomata is dependent on various cell types. The typical composition is a center of macrophages/histiocytes with lymphocytes at the border. The sequence of events leading to granuloma formation is regulated by various cell types and cytokines: While Th1-associated mechanisms promote granuloma development, it appears that regulatory T cells as well as M2 macrophages together with interleukin (IL)-10 and IL-13 lead to their dissociation and tissue healing. There is a strong correlation between structure and function of granulomas. Chronic inflammatory granulomatous skin diseases are primarily based on dysfunctional downmodulation of inflammatory processes that lead to and maintain granuloma formation.

[Leishmaniasis : Diagnosis and therapy]. / Leishmaniasis : Diagnostik und Therapie.

The delayed appearance of a papule after returning from travelling hints towards the diagnosis cutaneous leishmaniasis. Histologically, a granulomatous inflammatory response is seen, and using Giemsa staining, intracellular parasites can be visualized within histiocytes. Polymer chain reaction (PCR) from the tissue or subsequent cultures not only aids in excluding other differential diagnoses, but also in the identification of the causing Leishmania subspecies. The latter is important for the choice of the optimal therapeutic regimen.

Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity.

BACKGROUND: A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking. OBJECTIVES: To develop and validate a novel dynamic scoring system to assess the severity of HS. METHODS: A Delphi voting procedure was conducted among the members of the European Hidradenitis Suppurativa Foundation (EHSF) to achieve consensus towards an initial HS Severity Score System (HS4). Strengths and weaknesses of HS4 were examined by a multicentre prospective study. Multivariate logistic regression, discriminant analysis and receiver operating characteristic curves, as well as examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores, were engaged to recognize the variables for a new International HS4 (IHS4) that was established by a second Delphi round. RESULTS: Consensus HS4 was based on number of skin lesions, number of skin areas involved and Dermatology Life Quality Index (DLQI), and was evaluated by a sample of 236 patients from 11 centres. Subsequently, a multivariate regression model calculated adjusted odds ratios for several clinical signs. Nodules, abscesses and draining tunnels resulted as the scoring variables. Three candidate scores were presented to the second Delphi round. The resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. Cohen's kappa was fair (κ = 0·32) compared with Hurley classification, and moderate (κ = 0·49) compared with Expert Opinion. Correlation was good (ρ > 0·6) with Hurley classification, Expert Opinion, Physician's Global Assessment and Modified Sartorius score, and moderate for DLQI (ρ = 0·36). CONCLUSIONS: The novel IHS4 is a validated tool to dynamically assess HS severity and can be used both in real-life and the clinical trials setting.

[Granuloma annulare]. / Granuloma anulare.

Granuloma annulare is a benign, chronic inflammatory skin disease. Its pathogenesis is still unclear, but reports on infections as a trigger can be found. In addition, some authors reported an association with other systemic disease, e.g., cancer, trauma, and diabetes mellitus; however, these have not been verified. The clinical picture of granuloma annulare ranges from the localized form predominantly at the extremities to disseminated, subcutaneous, or perforating forms. Diagnosis is based on the typical clinical presentation which may be confirmed by a biopsy. Histologically, necrobiotic areas within granulomatous inflammation are typical. The prognosis of the disease is good with spontaneous resolution being frequently observed, especially in localized forms. Disseminated manifestations tend to persist longer, and recurrences are reported. When choosing between different therapeutic options, the benign disease character versus the individual degree of suffering and the potential therapy side effects must be considered. For local treatment, topical application of corticosteroids is most common. Disseminated forms can be treated systemically with corticosteroids for several weeks; alternatively, dapsone, hydroxychloroquine, retinoids, fumaric acid, cyclosporine, and anti-TNFα appear to be effective.

[Sarcoidosis : Organ involvement, diagnosis, current treatment]. / Sarkoidose : Organbeteiligung, Diagnostik, aktuelle Therapie.

Sarcoidosis is characterized by the appearance of noncausating, epitheloid cell granulomas, primarily in skin and lung. Hereditary disposition is well known; additional infection-associated triggers play a role for the development of inflammation mediated by T helper (Th)1 cells. Clinically, various disease courses can be observed that are characterized by the formation of skin papules at typical sites of the body which differ in their tendency to be associated with systemic organ involvement. Systemic disease without skin affections is also possible. The diagnosis is based on the typical clinical appearance, biopsy of affected tissue (e.g. skin, lung) and laboratory investigations. Additional systemic involvement needs to be excluded. In most cases, the disease is self-limited, but can also be life threatening due to organ fibrosis. The degree of (extra-)cutaneous involvement and level of discomfort are used to select the type of treatment, which ranges from topical immune suppressive agents to systemic therapy with corticosteroids. In nonresponders, additional modern immunosuppressive/immunomodulating therapeutic options are available.

[Significance of topical therapy in clinical situations. Location-dependent principles]. / Stellenwert der topischen Therapie in klinischen Behandlungssituationen. Lokalisationsspezifische Prinzipien.

Topical therapy remains an important domain of dermatology. The choice of the base or vehicle for topical therapy has to be appropriate for both the skin disorder and the localization. In cases with intact skin barrier (horny layer, lipid barrier) lipophilic formulations are more suitable because of superior penetration, whereas hydrophilic creams should be favored when facing more acute, weeping skin conditions. Because of location-specific variations in the macro- and micro-anatomy and the microbiota of the skin, the topical agent that is chosen must have quite specific properties in order to function optimally. These location-specific differences and potential therapeutic principles will be discussed in greater detail.

[Cutaneous leishmaniasis as travelers' disease. Clinical presentation, diagnostics and therapy]. / Kutane Leishmaniasis als Reisedermatose. Klinik, Diagnostik und Therapie.

Leishmaniasis is a disease with worldwide increasing incidence, which in Germany is almost exclusively observed in patients who have travelled to classical endemic regions such as the Mediterranean basin. Cause of the disease is an infection with protozoan parasites of the genus Leishmania, which are transmitted by sand flies and replicate intracellularly within mammalian hosts. Depending on the inoculated parasite (sub-) species and the immune status of the host, a local cutaneous, diffuse cutaneous, mucocutaneous or visceral form of leishmaniasis will develop. Cutaneous leishmaniasis, which frequently appears only weeks after the bite of a sand fly, starts with the formation of a papule, which subsequently can turn into a skin ulcer. The latter may heal spontaneously after months leaving behind a scar or persist as chronic, non-healing cutaneous leishmaniasis. If cutaneous leishmaniasis is suspected, a sterile skin biopsy followed by appropriate diagnostic measures in a specialized laboratory to identify the pathogen should be performed. For the decision on the type of therapy, several clinical parameters (e.g. number and localization of lesions, immune status) and, most importantly, the underlying parasite (sub-) species need to be considered. Therapy can consist of a variety of topical measures or systemic drug treatment. A modern and safe vaccine does not yet exist.

Resolving lesions in human cutaneous leishmaniasis predominantly harbour chemokine receptor CXCR3-positive T helper 1/T cytotoxic type 1 cells.

BACKGROUND: Cutaneous leishmaniasis (CL) is an epidemic disease affecting millions of individuals worldwide. Treatment options have several side-effects and a vaccine does not exist at present. OBJECTIVES: To translate information about protection against CL from mice to man, we studied the local immune response in CL skin biopsies and correlated these findings with clinical information. METHODS: The frequency of inflammatory cells was determined in skin biopsies of 20 patients diagnosed with CL using immunohistochemistry. In addition, the nature of the resulting adaptive immune response was assessed by (double) immunostaining against CD4 and chemokine receptors CXCR3 (T helper 1, Th1)/CCR4 (Th2). RESULTS: All lesions contained CD4+ and CD8+ T cells, B cells and CD68+ macrophages. CD1a+ epidermal Langerhans cells were absent above the centre of the lesions, but normally distributed in the surrounding tissue. Mast cell and CD56+ natural killer cell numbers were not affected. Interestingly, CCR4+ Th2 cells were not detected in any of the 20 samples. In contrast, the number of infiltrating CXCR3+ cells was high and the majority of these were CD4+ or CD8+ indicating that they represent interferon-gamma-producing Th1/T cytotoxic type 1 (Tc1) cells. Finally, these findings did not correlate with clinical information about the country where the infection was acquired, or age or sex of the patients. However, lesions that had already persisted for more than 6 months contained fewer CXCR3+ CD4 and CD8 T cells than those that had persisted for less than 6 months. CONCLUSIONS: Our data on the inflammatory infiltrate of human CL lesions underline the relevance of findings obtained in experimental models. Both Th1 and Tc1 cells appear to be critical for healing in CL in mouse and man.

The programmed death (PD)-1/PD-ligand 1 pathway regulates graft-versus-host-reactive CD8 T cells after liver transplantation.

Acute graft-versus-host disease (aGVHD) is a life-threatening complication after solid-organ transplantation, which is mediated by host-reactive donor T cells emigrating from the allograft. We report on two liver transplant recipients who developed an almost complete donor chimerism in peripheral blood and bone marrow-infiltrating T cells during aGVHD. By analyzing these T cells directly ex vivo, we found that they died by apoptosis over time without evidence of rejection by host T cells. The host-versus-donor reactivity was selectively impaired, as anti-third-party and antiviral T cells were still detectable in the host repertoire. These findings support the acquired donor-specific allotolerance concept previously established in animal transplantation studies. We also observed that the resolution of aGVHD was not accompanied by an expansion of circulating immunosuppressive CD4/CD25/FoxP3-positive T cells. In fact, graft-versus-host-reactive T cells were controlled by an alternative negative regulatory pathway, executed by the programmed death (PD)-1 receptor and its ligand PD-L1. We found high PD-1 expression on donor CD4 and CD8 T cells. In addition, blocking PD-L1 on host-derived cells significantly enhanced alloreactivity by CD8 T cells in vitro. We suggest the interference with the PD-1/PD-L1 pathway as a therapeutic strategy to control graft-versus-host-reactive T cells in allograft recipients.

Vaccinations against cutaneous Leishmania infection.

Cutaneous leishmaniasis is an endemic disease with increasing incidence, even in Europe. Recently, it has attracted more attention due to reactivation in immunocompromised hosts, e.g. in the context of HIV. Therapeutic options range from topical treatment to systemic therapy for more complex cases. A vaccine does not exist at present. Despite of several attempts, vaccine generation has proven to be difficult even though protective immunity against this obligate intracellular protozoan parasite is dependent on the development of antigen-specific CD4+ and CD8+ T cells capable of releasing IFN?. IFN?, in turn, activates phagocytic host cells to generate oxidative radicals and to eliminate the parasite. This review will describe the basic immunology leading to the development of protective immunity in infected individuals. In addition, the authors will focus on highlighting the different approaches utilized for vaccine development and describe what a efficient vaccine may consist of. Combined intensive research in the fields of basic parasitology and immunology may allow for the generation of an efficacious vaccine against this important human pathogen in the near future.

[Cutaneous leishmaniasis]. / Kutane Leishmaniasis.

Infections with Leishmania are increasing worldwide because of tourism and job-related travel; central Europe is no exception. Infections often first become apparent after return from an endemic region. Depending on the Leishmania species and the host immune status, different forms of cutaneous (CL), mucocutaneous (MCL) (L. brasiliensis complex) or visceral leishmaniasis (L. donovani as well as L. infantum) may develop. CL may heal spontaneously with scarring but can evolve into diffuse CL (with reduced immune response to L. amazonensis, L. guyanensis, L. mexicana or L. aethiopica) or into recurrent CL. Diagnostic criteria include travel to an endemic area as well as ulcerated plaques or nodules on an exposed site which show no tendency towards healing over 3-4 weeks. Differential diagnostic considerations include ecthyma, other infectious ulcers, and malignant neoplasms. The diagnosis is confirmed by finding Leishmania in a smear or tissue biopsy, as well as by culture. Therapy options range from topical treatment of simple CL of the Old World caused by L. major to systemic therapy which is needed for most complex cases of CL as well as MCL. Miltefosine is a less toxic option to replace the antimony compounds.

[Hypocomplementemic urticarial vasculitis syndrome. Successful therapy with intravenous immunoglobulins]. / Hypokomplementämisches Urtikaria-Vaskulitis-Syndrom. Erfolgreiche Therapie mit intravenösen Immunglobulinen.

Autoimmune diseases can initially present as chronic urticaria. We describe the course of a patient with hypocomplementemic urticarial vasculitis syndrome (HUVS) as well as his successful treatment with high-dose intravenous immunoglobulins (IVIG). HUVS was diagnosed clinically and confirmed by histology and laboratory studies. After only one cycle with IVIG (2 g/kg) all HUVS symptoms were significantly decreased.