Short Version of the Quality of Life Relevance-Acne Questionnaire.

INTRODUCTION: The goal of the present study was to develop a short version (SV) of the Quality of Life Relevance-Acne (QOLRELEVANCE-ACNE) based on the identified most relevant items for acne patients. METHODS: Members of the international internet group for acne patients were asked to fill in the short prototype version of the QOLRELEVANCE-ACNE. Internal consistency was measured using Cronbach's alpha. RESULTS: The answers of 684 acne patients were collected. The analysis revealed that the internal consistency of the instrument could be improved by removing a single item. That item was removed and the final four-item short version of the QOLRELEVANCE-ACNE-SV was formed. There is minimal or no overlapping of the QOLRELEVANCE-ACNE-SV with other brief forms of acne-specific HRQoL instruments. CONCLUSION: The four-item QOLRELEVANCE-ACNE-SV questionnaire was developed and showed good internal consistency. An international validation study of the QOLRELEVANCE-ACNE-SV will be performed.

Guidelines How to Integrate Surgery and Targeted Therapy with Biologics for the Treatment of Hidradenitis Suppurativa: Delphi Consensus Statements from an Italian Expert Panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.

The use of ultrasound and magnetic resonance imaging in the management of hidradenitis suppurativa: a narrative review.

Hidradenitis suppurativa (HS) is a chronic, inflammatory follicular skin disease that frequently affects the apocrine gland-bearing skin of the axillary, inguinal and anogenital regions. HS has a significant impact on the psychosocial health and quality of life of patients. Diagnosis of HS is typically clinical, and relies on the ability of physicians to recognize the signs of HS. However, lesions may present at the dermal and subcutaneous skin layers, which cannot be diagnosed by clinical examination alone. Further, the complexity of the clinical presentation of HS can lead to misdiagnosis and delay of diagnosis and appropriate treatment. Imaging is an important tool that can address these issues by detecting inflammatory activity and the early subclinical and dermal features of HS, and accurately characterizing lesional morphology, thereby informing on optimal therapeutic strategies. Overall, imaging is a key tool that can be used in conjunction with clinical examination to improve the management of HS by providing additional information to physicians, and thus optimize clinical decision making. In this narrative review, we provide an overview of the general role of imaging in the management of HS, and we illustrate HS-specific applications of two pertinent imaging modalities, ultrasound and magnetic resonance imaging. Finally, based on the literature, we summarize their uses in HS and provide considerations relating to standardizing the practise of ultrasound and effectively implementing the use of imaging in the management of HS.

Which Health-Related Quality of Life Items Most Affect Acne Patients?

BACKGROUND: Health-related quality of life (HRQoL) assessment in patients with acne is recommended by several national guidelines. There are several acne-specific HRQoL instruments. OBJECTIVES: Participants of the European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on QoL and Patient Oriented Outcomes (PO) and Acne, Rosacea, and Hidradenitis Suppurativa (ARHS) agreed to scrutinize aspects of existing acne-specific HRQoL instruments for their relevance in international study. METHODS: Consensus agreement on items related to QoL was reached after an independent assessment by seven experts from the EADV TFs on QoL and PO, and a list of 97 items was prepared and proposed to a group of acne patients. In order to have data from patients to check if any important topics were overseen, another group of acne patients from participating countries was asked to list how acne influenced different aspects of their lives. RESULTS: Based on results obtained from 601 acne patients from nine countries, most of the items and topics showed low relevance for acne patients especially during the previous month or shorter time periods. Based on percentage of relevance and factor analysis, short (6 items) and long (45 items) lists of the most relevant topics were formed. CONCLUSION: Most of the items and topics from the initial list showed low relevance for acne patients. None of the identified acne-specific HRQoL instruments contain all the items that were deemed most relevant to acne patients. For this reason, participating members of the EADV TFs on QoL and PO, and ARHs are in the process of developing a new acne-specific HRQoL instrument.

Registries, multicentre and genome-wide association studies in hidradenitis suppurativa.

The European Hidradenitis Suppurativa Foundation (EHSF) e.V. has taken several initiatives for collaborative studies. They result from the data of the European Registry of Hidradenitis Suppurativa (ERHS) based on the knowledge obtained from the regional Northern countries (HISREG) and Italian (IRHIS) registries and the real-world data generated from claims data from insurance databases. Multicentre studies, such as the Hidradenitis Suppurativa collaborative study of subtypes (HORUS) and the Global Hidradenitis Suppurativa Atlas (GHISA), are planned to provide an ideal complement to the register studies. Most recently, the role of EHSF as a coordinator or key player is being explored in multiple genetic studies, such as a genome-wide association study (GWAS) and the exome sequencing and cellular/molecular profiling project, which will speed up gene and drug discovery in HS.

Hidradenitis suppurativa: Morphologic and vascular study of nodular inflammatory lesions by means of optical coherence tomography.

Hidradenitis suppurativa (HS) is an inflammatory disease characterized by a recurrent-remission trend and clinical lesions that range from asymptomatic to inflamed, deep-seated nodules with scarring and suppuration. The aim of our study was to identify morphologic and vascular features of HS nodules by means of dynamic optical coherence tomography (D-OCT) and to define if they are correlated to patient endotype and risk of disease progression. A set of standardized clinical pictures and D-OCT images were acquired from 57 inflammatory nodules of 40 patients affected by HS. A set of 20 clinical and D-OCT images were acquired from 20 healthy volunteers as a control group. The comparison of D-OCT features among HS and control group was analysed. The correlation between HS patient endotype and D-OCT features of the lesions was calculated. D-OCT enabled to identify vascular and morphological aspects characterizing HS nodular inflammatory lesions. In addition, several D-OCT features were significantly different among distinct disease endotypes. The characterization of HS nodular inflammatory lesions through D-OCT, corresponding to blood vessel dilation and inflammatory associated hyper-vascularization, may have important clinical consequences in the assessment of HS risk of progression, therapeutic decisions and treatment efficacy monitoring.

Anti-COVID-19 measurements for hidradenitis suppurativa patients.

The reported incidence of COVID-19 among cohorts of patients with inflammatory bowel and skin diseases under treatment with biologicals is low. Treatment may further modify disease severity as some biological modifiers, such as anakinra, are also proposed for the management of COVID-19 patients potentially providing HS patients with an advantage. The above preliminary evidence suggests that hidradenitis suppurativa (HS) does probably not provide an increased susceptibility for COVID-19 and that any susceptibility is unlikely to be modified negatively by treatment with biologicals. On the occasion of its 10th International Conference, experts of the European Hidradenitis Suppurativa Foundation e.V. have prepared a consensus statement regarding anti-COVID-19 measurements for HS patients. Based on the available knowledge, patients with HS may be vaccinated against SARS-CoV2 and patients affected by metabolic syndrome constitute a high-risk group for COVID-19 and should be vaccinated at the earliest convenient point in time. HS patients on treatment with adalimumab can be vaccinated with non-living virus anti-SARS-CoV2 vaccines. A possible suboptimal effect of the vaccine may be suspected but might not be expected universally. The management of the biological treatment in HS patients is at the discretion of the dermatologist / responsible physician.

Irrelevance of Panton-Valentine leukocidin in hidradenitis suppurativa: results from a pilot, observational study.

Panton-Valentine leukocidin (PVL) appears to be a virulence factor which, among others, can exacerbate the pathogenicity of Staphylococcus aureus infections, especially inducing severe necrotic, deep-seated skin infections, abscesses, and recurrences. These peculiarities have some overlaps with hidradenitis suppurativa (HS). Our main aim was to assess if S. aureus producing PVL could have some role in influencing clinical features and/or course of HS, specifically in the suppuration and recurrence of lesions. This pilot, mono-centric, observational study included all adult subjects affected with HS consecutively referring to our HS clinic over a 3-month period. Clinically evident suppuration and at least 2 weeks wash out from any antibiotic were the main inclusion criteria. Purulent material from HS skin lesions was collected with swabs in order to isolate micro-organisms, with specific regard to S. aureus. Detection of PVL was performed by real-time quantitative PCR (RT-qPCR). We also analyzed purulent material from suppurative skin lesions other than HS, as a control. Thirty HS patients were included; 29 purulent lesions (96.7%) harbored at least one bacterial species. Five (16.7%) swab samples were positive for S. aureus, none of which was positive for PVL genes. Among the 30 purulent disorders included as controls, 8 (26.3%) were positive for S. aureus; of these, 4 strains (50%) expressed LPV. The study results seem to exclude the pathogenetic involvement of S. aureus producing PVL in HS; as a result, PVL does not seem to represent a potential target in the future development of HS treatments.

Tetracyclines and photosensitive skin reactions: A narrative review.

Tetracyclines are a group of broad-spectrum antibiotics largely employed in infectious, dermatological and surgical fields. Some adverse events may occur during treatment, including photosensitivity reactions, which are divided in phototoxic or photoallergic. We performed a systematic search on Pubmed, Cochrane and Embase from database inception to August 9, 2020 aim to summarize all available papers on photosensitive reactions related to tetracyclines in all clinical settings where they are used on human being. On the basis of our inclusion criteria, we selected only randomized controlled trials, open comparative trials and prospective cohort studies performed on both volunteers and patients, moreover we included a pharmacovigilance register. Thirty-eight articles met inclusion criteria, describing photo-sensitive effects due to doxycycline, minocycline, tetracycline, lymecycline, sarecycline, demethylchlortetracycline, chlortetracycline and metacycline, across six diagnoses (acne, Lyme disease, Gulf Veteran Illness, adbominal aortic aneurysms, traveler's diarrhea and pterygium) and several volunteers who were deliberately exposed to natural or artificial light sources. Not all drugs belonging to tetracyclines class are available to date, moreover the studies included lacked a homogeneous design and most of them involved a scarce number of patients, including reactions induced in volunteers during photo-testing. Available data on incidence, severity and clinical relevance of tetracyclines-related photo-sensitive reactions are scarce, heterogeneous and weak. What we can extrapolate is that some tetracyclines are more often related to phototoxic skin reactions than others and some of those seem to have a very low risk of phototoxicity.

The P2X7 Receptor Is Overexpressed in the Lesional Skin of Subjects Affected by Hidradenitis Suppurativa: A Preliminary Study.

BACKGROUND: P2X receptors (P2XRs) are plasma membrane channels involved in the modulation of immune responses. The role of the P2X7 receptor (P2X7R) has never been investigated in hidradenitis suppurativa (HS), which is a recurrent skin disease characterized by inflammatory nodules, scarring, and suppuration. OBJECTIVE: Our aim was to investigate by immunohistochemistry (IHC) P2X7R, NLRP3 (NOD-like receptor family, pyrin domain-containing 3), and interleukin-1ß (IL-1ß) expression in HS lesions compared to healthy control (HC) skin. METHOD: The intensity of IHC immunostaining was semi-quantitatively graded for keratinocytes, neutrophils, lymphocytes, and monocytes. Statistical significance was assessed by the Mann-Whitney U test, Cohen's κ coefficient, and χ2 test. RESULTS: A total of 59 samples, 31 from HS and 28 from HC, were collected and analysed. In skin keratinocytes, lymphocytes, and monocytes, but not in neutrophils, P2X7R and NLRP3 protein expression was significantly increased in HS versus the HC group. IL-1ß protein expression was also higher in HS versus the HC group both in skin keratinocytes and in the inflammatory infiltrate. Cohen's κ correlation coefficients for the expression of P2X7R versus NLRP3 or IL-1ß in skin keratinocytes were significant (κ = 0.43 and 0.34, respectively). The same association between P2X7R and NLRP3 or IL-1ß was confirmed by χ2 tests. CONCLUSION: P2X7R, NLRP3, and IL-1ß are overexpressed, and therefore the entire P2X7R/NLRP3/IL-1ß pro-inflammatory axis is likely overactive in the skin of HS patients. This observation might provide clues to the pathogenesis of this disease and suggest novel therapies and markers of disease activity.

The link between hidradenitis suppurativa and phylloid hypomelanosis in partial trisomy-13 mosaicism: New evidences and further genetic/pathogenetic insights.

Partial trisomy-13 mosaicism (PT13M) is a rare condition. Among its possible associated cutaneous features, phylloid hypomelanosis (PH), characterized by leaf-like macules reminiscent of floral ornaments in the form of round or oval spots and patches and oblong lesions, is typical. Two cases of PH associated with hidradenitis suppurativa (HS) have been already reported in the literature. We report a third child with PH due to PT13M associated with HS-like lesions limited to hypomelanotic regions. We hypothesize that follicular occlusion genes may be located in the duplicated part of chromosome 13.

Anger, Emotional Fragility, Self-esteem, and Psychiatric Comorbidity in Patients with Hidradenitis Suppurativa/Acne Inversa.

Hidradenitis suppurativa/acne inversa (HS) is one of the most debilitating inflammatory chronic skin diseases and it heavily impairs the emotional and relational life of the patients. Despite its clinical and epidemiological relevance, its psychological correlates are still largely unexplored. The aim of the present study was to investigate the psychological and emotional impact of HS, with a specific focus on psychiatric symptoms, particularly depression, suicidal ideation, self-esteem, anger, and some personality traits. Thirty eight patients diagnosed with HS (HS Group) were compared with a control group of 28 outpatients diagnosed with nevi (N Group) and assessed with psychometric questionnaires (GHQ-28, STAXI-2, BDI-II, BHS, RSES, EF Questionnaire, and I-R Questionnaire). Results showed significant differences between the two groups, with more psychiatric symptoms, lower self-esteem, and higher levels of state anger and of emotional fragility in HS patients. These findings suggest the evidence of a significant psychiatric comorbidity in HS and of a strong emotional impact of the disease.

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne.

Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.

Adult female acne and associated risk factors: Results of a multicenter case-control study in Italy.

BACKGROUND: The reasons for the appearance of acne in adulthood are largely unknown. OBJECTIVE: We explored the role of personal and environmental factors in adult female acne. METHODS: We conducted a multicenter case-control study in the outpatient departments of 12 Italian cities. Cases (n = 248) were consecutive women ≥25 years of age with newly diagnosed acne of any grade. Controls (n = 270) were females diagnosed with conditions other than acne. RESULTS: In multivariate analysis, a history of acne in parents (odds ratio [OR] = 3.02) or siblings (OR = 2.40), history of acne during adolescence (OR = 5.44), having no previous pregnancies (OR = 1.71), having hirsutism (OR = 3.50), being an office worker versus being unemployed or being a housewife (OR = 2.24), and having a high level of reported psychological stress (OR = 2.95) were all associated with acne. A low weekly intake of fruits or vegetables (OR = 2.33) and low consumption of fresh fish (OR = 2.76) were also associated with acne. LIMITATIONS: We did not establish an onset date for acne. Some of our associations may reflect consequences of established acne. CONCLUSION: Lifestyle factors may play an important role for acne development in adulthood, but their role should be further assessed in prospective studies.

New Atrophic Acne Scar Classification: Reliability of Assessments Based on Size, Shape, and Number.

BACKGROUND: Post-acne atrophic scarring is a major concern for which standardized outcome measures are needed. Traditionally, this type of scar has been classified based on shape; but survey of practicing dermatologists has shown that atrophic scar morphology has not been well enough defined to allow good agreement in clinical classification. Reliance on clinical assessment is still needed at the current time, since objective tools are not yet available in routine practice.
OBJECTIVES: Evaluate classification for atrophic acne scars by shape, size, and facial location and establish reliability in assessments.
METHODS: We conducted a non-interventional study with dermatologists performing live clinical assessments of atrophic acne scars. To objectively compare identification of lesions, individual lesions were marked on a high-resolution photo of the patient that was displayed on a computer during the clinical evaluation. The Jacob clinical classification system was used to define three primary shapes of scars 1) icepick, 2) boxcar, and 3) rolling. To determine agreement for classification by size, independent technicians assessed the investigators' markings on digital images. Identical localization of scars was denoted if the maximal distance between their centers was ≤ 60 pixels (approximately 3 mm). Raters assessed scars on the same patients twice (morning/afternoon). Aggregate models of rater assessments were created and analyzed for agreement.
RESULTS: Raters counted a mean scar count per subject ranging from 15.75 to 40.25 scars. Approximately 50% of scars were identified by all raters and ~75% of scars were identified by at least 2 of 3 raters (weak agreement, Kappa pairwise agreement 0.30). Agreement between consecutive counts was moderate, with Kappa index ranging from 0.26 to 0.47 (after exclusion of one outlier investigator who had significantly higher counts than all others). Shape classifications of icepick, boxcar, and rolling differed significantly between raters and even for same raters at consecutive sessions (P<.001 and P=0.4, respectively). Analysis showed only 65% of scars were identical in both sessions. We also found that there is a threshold of detection in terms of size, with poor agreement among investigators for very small scars (<2 mm). The repeatability of identification of scars ≥ 2.0 mm was acceptable, and we found that increasing scar size was positively correlated with agreement. Reliability was improved when only scars >2 mm were included. For smaller scars (<2 mm), inter-rater reliability was poor.
CONCLUSIONS: While intuitively it makes sense that describing scar morphology could guide treatment, we have shown that shape-based evaluations are subjective and do not readily yield strong agreement. Until there is a more objective way to evaluate morphology that is readily available to practicing clinicians, we propose that size should be considered a primary characteristic for scar classification systems. We further suggest classification of <2 mm, 2-4 mm, and >4 mm based on how the size would likely affect diagnostic and therapeutic choices. Finally, we recommend that scars <2 mm not be included in a clinical classification but should be evaluated by an objective method that may be refined in the future.

J Drugs Dermatol. 2016;15(6):693-702.

Isotretinoin-unresponsive acne as a sign of a congenital disorder: a case of 21-hydroxylase deficiency.

Acne is a multifactorial and common disorder among young people and a frequent reason for dermatology consultation. When moderate-to-severe acne is not responsive to conventional treatments, oral isotretinoin is a very effective solution. However, there are cases in which this treatment fails to produce the expected results. In this case, an 18-year-old male patient with acne, unresponsive to traditional acne therapies, experienced only a partial benefit from oral isotretinoin. Endocrinology consultation and hormonal work-up revealed androgen metabolism anomalies suggestive of a non-classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. In this case report, the authors discuss when to suspect, how to diagnose, and how to manage similar cases.

A Case of Dissecting Cellulitis of the Scalp, Hidradenitis Suppurativa, and Conglobate Acne Successfully Treated with Secukinumab.

Introduction: Dissecting cellulitis of the scalp (DCS) is a neutrophilic scarring alopecia typically presenting with pustules and fluctuant nodules, followed by suppuration and sinus tract formation. DCS is often associated with other diseases, such as hidradenitis suppurativa (HS) and conglobate acne (CA) which share similar pathogenetic mechanisms. Case Presentation: The authors report the case of a patient affected by a severe form of DCS, HS, and CA of the face. Previous treatments with isotretinoin, antibiotics, and adalimumab did not have a considerable efficacy. Off-label treatment with secukinumab showed a gradual improvement in the clinical presentation bringing to a reduction in the number of HS lesions and to an almost complete resolution of the inflammatory manifestations of DCS. Conclusion: Management of DCS is challenging and is typically based on retinoids which are considered the first line of treatment. The efficacy of biologic drugs, especially TNFα inhibitors, in severe and relapsing forms of DCS has been reported in recent literature. To our knowledge, only one case of isolated DCS treated with secukinumab is reported. No cases of concomitant DCS and HS, treated with this type of IL-17 inhibitor, have been described.