Outcome Measures for the Evaluation of Treatment Response in Hidradenitis Suppurativa for Clinical Practice: A HiSTORIC Consensus Statement.

Importance: Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines. Objective: To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied. Evidence Review: Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice. Findings: Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]). Conclusions and Relevance: An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting.

Clinical characteristics of pediatric hidradenitis suppurativa: a cross-sectional multicenter study of 140 patients.

Hidradenitis suppurativa (HS) rarely affects pediatric patients. The literature on pediatric HS patients is scarce. This is a cross-sectional study based on case note review or interviews and clinical examination of 140 pediatric patients undergoing secondary or tertiary level care. Patients were predominantly female (75.5%, n = 105) with a median age of 16. 39% reported 1st-degree relative with HS. Median BMI percentile was 88, and 11% were smokers (n = 15). Median modified Sartorius score was 8.5. Notable comorbidities found were acne (32.8%, n = 45), hirsutism (19.3%, n = 27), and pilonidal cysts (16.4%, n = 23). Resorcinol (n = 27) and clindamycin (n = 25) were the most frequently used topical treatments. Patients were treated with tetracycline (n = 32), or oral clindamycin and rifampicin in combination (n = 29). Surgical excision was performed in 18 patients, deroofing in five and incision in seven patients. Obesity seemed to be prominent in the pediatric population and correlated to parent BMI, suggesting a potential for preventive measures for the family. Disease management appeared to be similar to that of adult HS, bearing in mind that the younger the patient, the milder the disease in majority of cases.

Hidradenitis Suppurativa in Sweden: A Registry-Based Cross-Sectional Study of 13,538 Patients.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition with nodules and fistula formation and scarring. It is a debilitating disease with a severe negative impact on quality of life. There is a need for increased knowledge about the social and lifestyle characteristics of patients with HS in general, and pregnant women in particular. OBJECTIVES: The aims of this study were to investigate and describe social characteristics and comorbidity in all HS patients in Sweden as well as to study the prevalence of lifestyle factors associated with negative impact on health and pregnancy in Swedish pregnant women with HS. METHODS: A registry-based cross-sectional study was performed by record linkage between Swedish registers covering the entire population. A cohort of 13,538 HS patients diagnosed with HS in specialised care during the years 2001-2014 and a subgroup of 1,368 HS patients who had undergone pregnancy during 2010-2015 were defined and described. Aggregated public data on the entire Swedish population and all pregnancies in 2014 were described for reference. RESULTS: The HS population had an average age of 44 years on December 31, 2014. The prevalence of HS was 0.14%. In comparison to the Swedish reference population the HS patients were more often women, unmarried (36 vs. 44% married), and had lower education (68 vs. 82% with an upper-secondary school degree or higher) and lower income (39 vs. 16% made SEK <100,000 a year). Comorbidity was 3% for inflammatory bowel disease and 8% for type 2 diabetes. The subgroup analysis showed high prevalence of overweight, obesity, and smoking in pregnant women with HS. CONCLUSIONS: The results from this comprehensive characterisation of Swedish HS patients may be used to improve preventive measures, information, and care for this vulnerable group.

[Cutaneous mastocytosis - update and clinical guidelines]. / Mastocytos i huden ­ uppdatering av kunskapsläget och riktlinjer för handläggning.

Mastocytosis is a rare and multifaceted disease group characterized by mast cell accumulation in the skin and/or internal organs. In its most common form solitary or widespread, often itchy, red-brown skin lesions appear in childhood or during adulthood (cutaneous mastocytosis). The skin lesions are not always easy to recognize by medical professionals; hence, a correct diagnosis is often delayed. In children, the lesions tend to resolve before puberty, whereas most post-adolescent patients experience a chronic course combined with extra-cutaneous mast cell infiltration (systemic mastocytosis). Therefore, adult patients with cutaneous mastocytosis should be examined for signs of systemic involvement. This article describes the symptoms and signs in cutaneous mastocytosis, and provides guidelines based on international consensus documents. In addition, a newly updated classification of different forms of cutaneous mastocytosis is given.

Photochemotherapy and Graft-versus-Leukemia Reaction in Acute Leukemia: Tumor Immunity and Survival Are Dependent on Timing of Photochemotherapy of the Skin.

BACKGROUND: Cure of acute leukemia after transplantation is mediated by the grafted cells. We investigated the graft-versus-leukemia effect (GVL) in patients with cutaneous acute graft-versus-host disease (GVHD) treated with photochemotherapy (psoralen and ultraviolet light type A). METHOD: Forty-seven patients with acute leukemia were followed 5,000 days after transplantation to assess survival and GVL by multivariate analysis. The primary predictor was time to treatment of cutaneous acute GVHD by photochemotherapy separated into treatment start during the first week of acute GVHD versus after the first week of acute GVHD. RESULTS: Photochemotherapy started after the first week of acute GVHD predicted GVL with a hazard ratio (HR) of 3.94 (95% confidence interval, CI, 1.67-9.33, p = 0.0018) and survival with preserved GVL with an HR of 2.63 (95% CI 1.30-5.32, p = 0.007). The effects on GVL and survival with preserved GVL were present regardless of whether the patients were transplanted in remission or relapse (p < 0.05). Chronic GVHD came earlier in the group that started photochemotherapy after 1 week of acute GHVD, but chronic GVHD did not increase the GVL. CONCLUSION: The timing of photochemotherapy after cutaneous acute GVHD may direct the GVL and predict long-term leukemia-free survival.

Intralesional triamcinolone for flares of hidradenitis suppurativa (HS): A case series.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle. Standard practice of managing acute flares with corticosteroid injection lacks scientific evidence. OBJECTIVE: We sought to assess the outcomes of routine treatment using intralesional triamcinolone (triamcinolone acetonide 10 mg/mL) in the management of acute flares in HS. METHODS: This was a prospective case series evaluating the effect of intralesional corticosteroids for alleviation of acute flares in HS. Physician- and patient-reported outcomes were noted. RESULTS: Significant reductions in physician-assessed erythema (median score from 2-1, P < .0001), edema (median score from 2-1, P < .0001), suppuration (median score from 2-1, P < .0001), and size (median score from 3-1, P < .0001) was demonstrated at follow-up. A significant difference in patient-reported pain visual analog scale scores occurred after 1 day (from 5.5-2.3, P < .005) and from day 1 to day 2 (from 2.3-1.4, P < .002). LIMITATIONS: Small study size, open single-arm design, and short follow-up time are the limitations of this study. CONCLUSION: Intralesional injection of corticosteroids is perceived as beneficial by physicians and patients in the management of HS flares by reducing pain after 1 day and signs of inflammation approximately 7 days later.

Photochemotherapy of Cutaneous Graft-versus-Host Disease May Reduce Concomitant Visceral Disease.

BACKGROUND: Photochemotherapy may be used to treat cutaneous graft-versus-host disease (GvHD). Animal models show that in the days after photochemotherapy and antigen provocation, cells with an antigen-specific suppressive phenotype are elicited in the lymphoid organs. In GvHD, host antigens are present not only in the skin treated by photochemotherapy but also in the visceral tissues. OBJECTIVE: The aim of this paper was to evaluate the effect on visceral acute GvHD (aGvHD) of photochemotherapy of the skin. METHODS: We retrospectively evaluated 33 patients with aGvHD of the skin, the liver, and/or the gastrointestinal tract treated with photochemotherapy for their aGvHD of the skin and did a long-term follow-up of 10 years on survival. RESULTS: The complete response (CR) to photochemotherapy was 39%, the complete and partial response was 64% and the 6-month survival was 64%. Total body irradiation (TBI) before hematopoietic stem cell transplantation predisposed for CR of aGvHD of the liver and the gastrointestinal tract (p = 0.045). In the TBI group, the accumulated dose (numbers of treatments) for CR of visceral aGvHD increased with the body surface area affected by disease, from 8 (min-max: 5-14) for skin disease stage 1 to 10.5 (6-33) for stage 2 and 13 (11-21) for stage 3 (p = 0.04). Skin disease stage 1 showed a trend to be associated with CR in visceral disease at 28, 56, and 100 days (p = 0.07). Overall CR in visceral disease predicted a better 10-year overall survival (p = 0.0036). Finally, after TBI aGvHD of the gastrointestinal tract without anti-thymocyte globulin (ATG), clearance of T cells and dendritic cells responded better than aGvHD of the liver and aGvHD of the gastrointestinal tract with ATG (p = 0.01). CONCLUSION: Photochemotherapy after ionizing irradiation regulates the cell-mediated immunity in the viscera, and the systemic efficacy increases when the skin itself is less affected by disease. ATG modulates the regulatory effect of the gastrointestinal tract.

The ABC of Hidradenitis Suppurativa: A Validated Glossary on how to Name Lesions.

BACKGROUND: The precise clinical description of skin lesions observed in some patients with hidradenitis suppurativa (HS) can be extremely difficult. OBJECTIVE: Establishing a validated glossary of terms allowing the best possible description of lesions observed in HS patients. MATERIAL AND METHODS: Five international experts of HS were to assess a series of 25 photos representing typical lesions of this disorder. For each photo, the experts were asked whether naming of the lesions was possible or not and, if yes, by using which noun. Agreement of their responses was calculated using Fleiss's kappa index. Using a Delphi strategy, photos with disagreement were discussed, and photos were reevaluated on the next day. In case of agreement on the impossibility of naming some clinical situations, new terms, to be included into the glossary, were agreed upon. RESULTS: After the first round of photos, agreement between the experts was poor with a kappa index of only 0.33 (95% CI 0.22-0.46). After extensive discussion of cases with disagreement, the kappa index increased on day 2 to 0.75 (95% CI 0.60-0.87), allowing to conclude on good interobserver agreement on terminology. Furthermore, a few clinical situations were identified in which naming with established semantics is so far not possible. For these situations, the terms 'multicord', 'multipore', 'multitunnel' and 'retraction' were defined. DISCUSSION: This is the first validation of clinical terms used to describe lesions in patients with HS. This should be helpful in better defining the clinical phenotypes observed in this disorder.

The Microbiology of Hidradenitis Suppurativa.

Although the clinical presentation of Hidradenitis Suppurativa (HS) is strongly reminiscent of bacterial infection, the role of bacteria remains controversial. Studies have isolated an array of different bacterial specimens as well as biofilm formation in lesional HS skin. Consistent findings of Gram-positive cocci and -rods including Staphylococus aureus, Coagulase-negative staphylococci (CoNS) and Corynebacterium species (spp) in deep tissue samples have been demonstrated in HS. Although efficacy of antibiotics, i.e., rifampicin, clindamycin or tetracycline may support a microbial role in disease pathogenesis, the most often isolated bacterial specimens are commensal bacteria (CoNS).

[Treated patients in survey: High satisfaction with botulinum toxin in palmar hyperhidrosis]. / Behandlade patienter i enkätundersökning:--Hög nöjdhet med botulinumtoxin vid palmar hyperhidros.

When debilitating, hyperhidrosis can be seen as a disease and not just as a symptom. It is most often a primary condition but can be secondary to other diseases. Aluminum chloride products are the initial treatment modality for palmar hyperhidrosis followed by anticholinergics, iontophoresis and botulinum toxin. The Dermatology Department of the Karolinska University Hospital in Stockholm, Sweden treated 151 patients at 289 visits with botulinum toxin for palmar hyperhidrosis during a two year period (2012-2013). It was found that botulinum toxin had good effect, which lasted between two and five months in 72% of cases. Muscle weakness (pincer grip) was reported at 41% of return visits and was present for less than one to four weeks in 62% of cases. At 56% of return visits, no side effects of botulinum toxin were reported. 90% of patients surveyed thought that botulinum toxin worked well or very well for their condition and 99% valued the treatment they received at the clinic as good to excellent.

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.

Microbiology of hidradenitis suppurativa (acne inversa): a histological study of 27 patients.

Hidradenitis suppurativa (acne inverse) (HS) is a chronic skin disease primarily affecting hair follicles. The aetiology of HS is unknown, but infection is believed to play some role. This retrospective study investigated the microbial colonization directly in skin appendices in HS skin samples. Archival samples from 27 patients with HS were screened by immunofluorescence labelling with monoclonal and polyclonal antibodies against Gram-positive bacteria, Propionibacterium acnes and Propionibacterium granulosum. Fluorescence in situ hybridization was used for further species identification of Staphylococcus spp. Overall, 17 patients (63%) were found positive for bacterial colonization. Of these, 15 showed colonization in hair follicles and/or sinus tracts. The most commonly identified bacteria were DAPI labelled coccoids that were seen in 71% of the positive patients in the form of biofilms and microcolonies. P. acnes was found as biofilms in hair follicles of two patients. Staphylococcus aureus and coagulase-negative staphylococci were not detected in any sample. The results of this study indicate a common bacterial presence in HS skin lesions. Bacterial biofilms are not uncommon and their pathogenic role needs further evaluation.

PGP 9.5 distribution patterns in biopsies from early lesions of atopic dermatitis.

Peripheral nerve fibres are often increased in lesional skin of atopic dermatitis (AD) patients. We attempted to study nerve fibre profiles, using PGP 9.5 as neuronal marker, in early AD lesions in 10 patients, as compared to non-lesional skin in the same patients and skin from healthy controls. The number of PGP 9.5-positive nerve fibre profiles was not different in the biopsies taken from normal-looking AD skin and healthy controls. The total number of PGP 9.5-positive nerve fibre profiles in the whole skin sections was higher in both the epidermis and the dermis in the group of skin biopsies taken from early lesions of AD patients. Further, the number of epidermal PGP 9.5-positive dendritic cells was increased in AD skin. It seems reasonable that PGP 9.5-positive nerve fibres and PGP 9.5-positive dendritic cells have pathological roles in AD. The findings might serve as a basis for further studies in evaluating novel diagnostic and therapeutic approaches.

Treatment of seborrhoeic dermatitis of the scalp with a topical solution of urea, lactic acid, and propylene glycol (K301): results of two double-blind, randomised, placebo-controlled studies.

Alternative treatments for seborrhoeic dermatitis are needed because of the increasing risk of anti-fungal resistance to existing therapies. To investigate the efficacy, safety and tolerability of topical scalp treatment with K301 solution. Two multi-centre, randomised, double-blind studies were conducted. Study I: 4 weeks of once-daily treatment with either one form of K301 (a or b) or placebo, followed by 4 weeks of maintenance treatment three times-per-week. Study II: 4 weeks of K301 (a) or placebo once-daily. Study I: 98 patients enrolled (K301a + b, n = 51; placebo, n = 47) and 83 completed; 201 entered Study II (K301a, n = 136; placebo, n = 65) and 195 completed. Erythema and desquamation sum score at 4 weeks, mean (SD) values were 2.4 (2.0) for K301a + b and 3.2 (2.2) for placebo in Study I (P = 0.025) and 2.5 (1.9) for K301a and 3.2 (1.8) for placebo in Study II (not significant). In both studies, 4-week desquamation scores were significantly improved for K301 vs. placebo (P < 0.05). Both studies showed significant improvements in symptomatic investigator and patient assessments for K301 over placebo after 4 weeks (P < 0.05). Treatment-related adverse events were generally mild and included some smarting or burning upon application. The K301 was well tolerated and associated with clinically meaningful improvements in seborrhoeic dermatitis endpoints.

Cutaneous PGP 9.5 distribution patterns in hidradenitis suppurativa.

The aim of this study was to investigate the presence and density of the nerve fibre-marker protein gene product 9.5 (PGP 9.5), with immunohistochemistry, in skin from patients with hidradenitis suppurativa (HS). Punch biopsies were obtained from 16 patients; 10 with involvement of the groin and six with axillary disease. Specimens were taken from HS lesions in the groin or axilla, clinically non-involved skin and from 12 healthy control subjects. Coded slides were observed in the microscope and PGP 9.5 positive nerve fibre profiles (profiles) as well as PGP 9.5 positive cells (cells) were counted. The overall impression was that the median number of profiles was decreased in lesional epidermis, yet statistically significant only in the groin (p = 0.0014). The median number of profiles in dermis was significantly decreased in lesional skin of the axilla, whereas in the groin there were contradictory findings with significantly increased number of profiles in upper dermis and non-significant in mid and lower dermis. The number of cells with strong immunofluorescence was few or absent in epidermis, but increased in dermis in the lesional skin. This difference was statistically significant throughout the dermis in specimens from the groin (p < 0.01) and showed the same trend, although not significant, in the axilla. The PGP 9.5 immunofluorescent cells were not yet further investigated, so it is not exactly known what cell type they represent. In conclusion, despite several study limitations, the findings indicate that PGP 9.5 positive nerve fibres could be involved in the pathogenesis of HS. Both regarding the profiles and the cells, further studies remain to show if these differences are primary events, or secondary to e g chronic inflammation, which is considered a major issue of HS.

Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial.

This multicentre, randomized study compared photodynamic therapy using topical methyl aminolaevulinate (MAL PDT), a non-invasive modality, with cryotherapy for treatment of superficial basal cell carcinoma. Sixty patients with 114 lesions were treated with MAL cream (160 mg/g) applied for 3 hours before illumination (570-670 nm, light dose 75 J/cm) (1 session), and 58 with 105 lesions received cryotherapy (2 freeze-thaw cycles). Patients with an incomplete response at 3 months received 2 further MAL PDT sessions (n = 20) or repeat cryotherapy (n = 16). 100 lesions treated with MAL PDT and 93 lesions treated with cryotherapy were in complete response at 3 months after the last treatment and evaluable for recurrence over 5 years. There was no difference in 5-year recurrence rates with either treatment (20% with cryotherapy vs. 22% with MAL PDT, p = 0.86). However, more patients had an excellent cosmetic outcome with MAL PDT (60% vs. 16% with cryotherapy, p = 0.00078). These results provide support for the use of MAL PDT as a non-invasive, selective treatment alternative for primary superficial basal cell carcinoma.