Development and validation of IHS4-55, an IHS4 dichotomous outcome to assess treatment effect for hidradenitis suppurativa.

BACKGROUND: Validated, inclusive and easy-to-use outcomes for hidradenitis suppurativa are essential both in the clinical trial setting and clinical practice. The continuous IHS4 is a validated tool that dynamically assesses nodules/abscesses/draining tunnels and classifies disease severity as mild/moderate/severe. However, dichotomous outcomes are often required for clinical trials reporting. OBJECTIVE: To develop and validate a dichotomous outcome based on IHS4 that can be used in clinical trial settings and day-to-day clinical practice. METHODS: De-identified data from the PIONEER-I and -II studies were accessed through Vivli. Potential IHS4 thresholds were analysed using baseline to Week 12 data from adalimumab- and placebo-treated hidradenitis suppurativa patients in the PIONEER-I trial. The final threshold was chosen based on its ability to discriminate between patients treated with adalimumab or placebo and its association with reduction in inflammatory lesions. The final threshold was validated using data from baseline to Week 12 from adalimumab- and placebo-treated hidradenitis suppurativa patients in both the PIONEER-II and the combined PIONEER-I and -II studies. RESULTS: The best performing cut-off for the IHS4 was a 55% reduction of the IHS4 score (IHS4-55). Patients who achieved the IHS4-55 had an odd's ratio of 2.00 [95%-CI 1.26-3.18, p = 0.003], 2.79 (95%-CI 1.76-4.43, p < 0.001) and 2.16 (95%-CI 1.43-3.29, p < 0.001) for being treated with adalimumab rather than placebo in PIONEER-I, PIONEER-II and the combined dataset, respectively. Additionally, the achievement of the IHS4-55 was associated with a significant reduction in inflammatory nodules, abscesses and draining tunnels in all analysed datasets. CONCLUSIONS: IHS4-55, a novel dichotomous IHS4 version, based on a 55% reduction of the total score was developed. The IHS4-55 performs similarly to the HiSCR in discriminating between adalimumab- and placebo-treated hidradenitis suppurativa patients and shows significant associations with reductions in lesion counts. Moreover, the IHS4-55 addresses some of the HiSCR drawbacks by dynamically including draining tunnels in a validated manner. By allowing the analysis of hidradenitis suppurativa patients with an abscess and nodule count below 3 but many draining tunnels, this outcome measure will improve inclusivity in clinical trials.

Surgical Treatment in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, progressive inflammatory disorder of follicular occlusion with pubertal onset that presents as painful inflammatory nodules, sinus tracts, and tunnelling in apocrine-gland-rich areas, such as the axilla, groin, lower back, and buttocks. The disease course is complicated by contractures, keloids, and immobility and is often associated with a low quality of life. It is considered a disorder of follicular occlusion with secondary inflammation, though the exact cause is not known. Management can often be unsatisfactory and challenging due to the chronic nature of the disease and its adverse impact on the quality of life. A multidisciplinary approach is key to prompt optimal disease control. The early stages can be managed with medical treatment, but the advanced stages most likely require surgical intervention. Various surgical options are available, depending upon disease severity and patient preference. In this review an evidence-based outline of surgical options for the treatment of HS are discussed. Case reports, case series, cohort studies, case-control studies, and Randomized Clinical Trials (RCT)s available in medical databases regarding surgical options used in the treatment of HS were considered for the review presented in a narrative manner in this article.

Achieving Hidradenitis Suppurativa Response Score is Associated with Significant Improvement in Clinical and Patient-reported Outcomes: Post Hoc Analysis of Pooled Data From PIONEER I and II.

Hidradenitis Suppurativa Clinical Response (HiSCR), is a validated tool that has been used to assess the efficacy of adalimumab among patients with hidradenitis suppurativa. We evaluated the clinical meaning of HiSCR by relating it to patient-reported outcomes to give further context to its achievement in a post hoc analysis of integrated data from two phase 3 clinical trials (PIONEER I and II). Pooling placebo and active treatment arms, 39% of patients (245/629) achieved HiSCR at week 12. Irrespective of treatment, significantly (p <0.05) more HiSCR responders than non-responders experienced clinically meaningful improvement in Dermatology Life Quality Index (60.5% vs 30.4%), Pain Numeric Rating Scale (46.9% vs 19.9%), hidradenitis suppurativa quality of life (49.4% vs 26.9%), work-related performance (52.6% vs 37.7%), and non-work-related performance (59.5% vs 33.3%). Clinically meaningful outcomes in hidradenitis suppurativa are more likely to be attained in patients achieving HiSCR level improvement.

Evidence-based approach to the treatment of hidradenitis suppurativa/acne inversa, based on the European guidelines for hidradenitis suppurativa.

Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by painful, recurrent nodules and abscesses that rupture and lead to sinus tracts and scarring. To date, an evidence-based therapeutic approach has not been the standard of care and this is likely due to the lack of evidence based treatment guidelines. The purpose of this study was to promote a holistic evidence-based approach which implemented Level of Evidence and Strength of Recommendation for the treatment of HS. Based upon the European Dermatology Forumguidelines for the management of HS, evidence-based approach was explored for the treatment of HS. The diagnosis of HS should be made by a dermatologist or other healthcare professional with expert knowledge in HS. All patients should be offered adjuvant therapy as needed (pain management, weight loss, tobacco cessation, treatment of super infections, and application of appropriate dressings). The treating physician should be familiar with disease severity scores, especially Hurley staging, physician global assessment and others. The routine use of patient'reported outcomesincluding DLQI, itch and pain assessment (Visual Analogue Scale) is strongly recommended. The need for surgical intervention should be assessed in all patients depending upon type and extent of scarring, and an evidence-based surgical approach should be implemented. Evidence-based medical treatment of mild disease consists of topical Clindamycin 1 % solution/gel b.i.d. for 12 weeks or Tetracycline 500 p.o. b.i.d. for 4 months (LOE IIb, SOR B), for more widespread disease. If patient fails to exhibit response to treatment or for a PGA of moderate-to-severe disease, Clindamycin 300 p.o. b.i.d. with Rifampicin 600 p.o. o.d. for 10 weeks (LOE III, SOR C) should be considered. If patient is not improved, then Adalimumab 160 mg at week 0, 80 mg at week 2; then 40 mg subcutaneously weekly should be administered (LOE Ib, SOR A). If improvement occurs then therapy should be maintained as long as HS lesions are present. If the patient fails to exhibit response, then consideration of second or third line therapy is required. A growing body of evidence is being published to guide the treatment of HS. HS therapy should be based upon the evaluation of the inflammatory components as well as the scarring and should be directed by evidence-based guidelines. Treatment should include surgery as well as medical treatment. Future studies should include benefit risk ratio analysis and long term assessment of efficacy and safety, in order to facilitate long term evidence based treatment and rational pharmacotherapy.

Randomized Controlled Trials for the Treatment of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease. Several treatment modalities are available, but most of them lack high-quality evidence. A systematic search was performed to identify all randomized controlled trials for the treatment of HS in order to review and evaluate the evidence. Recommendations for future randomized controlled trials include using validated scores, inclusion of patient rated outcomes, and thorough report of side effects. Evidence for long-term treatment and benefit/risk ratio of available treatment modalities is needed in order to enhance evidence-based treatment in daily clinical practice. Combining surgery with antiinflammatory treatment warrants further investigation.

Disseminated refractory pyoderma gangraenosum during an ulcerative colitis flare. Treatment with infliximab.

BACKGROUND: Pyoderma gangraenosum is an immune-mediated, inflammatory, neutrophilic dermatosis of unknown etiology, which represents one of the extraintestinal manifestations of inflammatory bowel disease. It is a rare disease that occurs in less than 1% of patients with inflammatory bowel disease and with the same ratio in patients with Crohn's disease and ulcerative colitis. MAIN OBSERVATIONS: A 36-year-old woman was diagnosed with ulcerative colitis 6 years before admission to our dermatology department with an acute disseminated pyoderma gangraenosum with mucosal involvement, during a flare of ulcerative colitis. Disease progression was interrupted by intravenous administration of the tumor necrosis factor-α inhibitor infliximab at 5 mg/kg at weeks 0, 2, and 6 (1st cycle) and every 8 weeks thereafter. Improvement of intestinal, skin and oral manifestations was evident already after the 1st cycle of treatment and has been maintained since (at least 16 months). CONCLUSIONS: This case report is one of very few on disseminated pyoderma gangraenosum with oral involvement complicating ulcerative colitis, where infliximab was shown to have a rapid efficacy on skin, mucosal and bowel symptoms.

Hidradenitis Suppurativa/Acne Inversa: Criteria for Diagnosis, Severity Assessment, Classification and Disease Evaluation.

BACKGROUND: Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating disease, which inflicts a significant burden on patients and is associated with comorbid disorders, such as significantly reduced quality of life, depression, stigmatization, inactivity, working disability, impairment of sexual health and several cardiovascular risk factors. AIMS/METHODS: To implement an expert consensus on the diagnostic criteria, severity and classification assessment, and an assessment of anti-inflammatory treatment effectiveness based on current evidence. RESULTS: This article provides criteria for diagnosis, severity assessment, classification and evaluation of HS patients. CONCLUSION: The provided criteria can be used as tools for the promotion of uniformity in HS evaluation and facilitation of early and timely identification and referral in the primary care setting and thorough and efficient evaluation in daily clinical practice.

Sentinel lymph node biopsy followed by lymph node dissection for localised primary cutaneous melanoma.

BACKGROUND: Melanoma is the leading cause of skin cancer-associated mortality. The vast majority of newly diagnosed melanomas are confined to the primary cutaneous site. Surgery represents the mainstay of melanoma treatment. Treatment strategies include wide excision of the primary tumour and sentinel lymph node biopsy (SLNB) to assess the status of the regional nodal basin(s). SLNB has become an important component of initial melanoma management providing accurate disease staging. OBJECTIVES: To assess the effects and safety of SLNB followed by completion lymph node dissection (CLND) for the treatment of localised primary cutaneous melanoma. SEARCH METHODS: We searched the following databases up to February 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2015, Issue 1), MEDLINE (from 1946), EMBASE (from 1974), and LILACS ((Latin American and Caribbean Health Science Information database, from 1982). We also searched the following from inception: African Index Medicus, IndMED of India, Index Medicus for the South-East Asia Region, and six trials registers. We checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We searched ISI Web of Science Conference Proceedings from inception to February 2015, and we scanned the abstracts of major dermatology and oncology conference proceedings up to 2015. SELECTION CRITERIA: Two review authors independently assessed all RCTs comparing SLNB followed by CLND for the treatment of primary localised cutaneous melanoma for inclusion. Primary outcome measures were overall survival and rate of treatment complications and side effects. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and analysed data on survival and recurrence, assessed risk of bias, and collected adverse effect information from included trials. MAIN RESULTS: We identified and included a single eligible trial comparing SLNB with observation and published in eight different reports (from 2005 to 2014) with 2001 participants. This did not report on our first primary outcome of overall survival. The study did report on the rate of treatment complications. Our secondary outcomes of disease-specific and disease-free survival, local recurrence and distant metastases were reported. There were 1347 participants in the intermediate-thickness melanoma group and 314 in the thick melanoma group.With regard to treatment complications, short-term surgical morbidity (30 days) in 1735 participants showed no difference between SLNB and observation (risk ratio [RR] 1.11; 95% confidence interval [CI] 0.9 to 1.37) for wide excision of the tumour site but favoured observation for complications related to the regional nodal basin (RR 14.36; 95% CI 6.74 to 30.59).The study did not report the actual 10-year melanoma-specific survival rate for all included participants. Instead, melanoma-specific survival rates for each group of participants: intermediate-thickness melanoma (defined as 1.2 to 3.5 mm) and thick melanomas (defined as 3.50 mm or more) was reported.In the intermediate-thickness melanoma group there was no statistically significant difference in disease-specific survival between study groups at 10 years (81.4 ± 1.5% versus 78.3 ± 2.0%, hazard ratio [HR] 0.84; 95% CI 0.65 to 1.09). In the thick melanoma group, again there was no statistically significant difference in disease-specific survival between study groups at 10 years (58.9.3 ± 4.1% versus 64.4 ± 4.6%, HR 1.12; 95% CI 0.77 to 1.64). Combining these groups there was some heterogeneity (I² = 34%) but the total HR was not statistically significant (HR 0.92; 95% CI 0.74 to 1.14). This study failed to show any difference for its stated primary outcome.The summary estimate for disease-free survival at 10 years favoured SLNB over observation in participants with intermediate-thickness and thick melanomas (HR 0.75; 95% CI 0.63 to 0.89).With regard to the rate of local and regional recurrence as the site of first recurrence, a benefit of SLNB uniformly existed in both groups of participants with intermediate-thickness and thick melanomas (RR 0.56; 95% CI 0.45 to 0.69). This is in contrast with a uniformly unfavourable effect of SLNB with regard to the rate of distant metastases as site of first recurrence, in both groups of participants with intermediate-thickness and thick melanomas (HR 1.33; 95% CI 1.03 to 1.72). AUTHORS' CONCLUSIONS: We contacted the trial authors querying the lack of data on overall survival which was the primary outcome of their important study. They stated "there are numerous additional analyses that have yet to be reported for the trial". We expect that overall survival data will be available in a future update of this review.Disease-free survival and rate of local and regional recurrence favoured SLNB in both groups of participants with intermediate-thickness and thick melanomas but short-term surgical morbidity was higher in the SLNB group, especially with regard to complications in the nodal basin.The evidence for the outcomes of interest in this review is of low quality due to the risk of bias and imprecision of the estimated effects. Further research may have an important impact on our estimate of the effectiveness of SLNB in managing primary localised cutaneous melanoma. Currently this evidence is not sufficient to document a benefit of SLNB when compared to observation in individuals with primary localised cutaneous melanoma.

Interventions for melanoma in situ, including lentigo maligna.

BACKGROUND: Malignant melanoma is a form of skin cancer associated with significant mortality once it has spread beyond the skin. Melanoma in situ (MIS) is the earliest histologically recognisable stage of malignant melanoma and represents a precursor of invasive melanoma. Lentigo maligna (LM) represents a subtype of pre-invasive intraepidermal melanoma associated specifically with chronic exposure to ultraviolet (UV) radiation. Over the past two decades, the incidence of MIS has increased significantly, even more than the invasive counterpart. There are several treatment options for MIS, but no consensus exists on the best therapeutic management of this condition. OBJECTIVES: To assess the effects of all available interventions, surgical and non-surgical, for the treatment of melanoma in situ, including LM. SEARCH METHODS: We searched the following databases up to November 2014: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 10), MEDLINE (from 1946), Embase (from 1974), LILACS (from 1982), African Index Medicus (from inception), IndeMED of India (from inception), and Index Medicus for the South-East Asia Region (IMSEAR) (from inception). We scanned the references of included and excluded studies for further references to relevant trials and searched five trials registries. We checked the abstracts of major dermatology and oncology conference proceedings, and we shared our lists of included and excluded studies with industry contacts and other experts in the field of melanoma to try to identify further relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCT) on the management of MIS, including LM, that compared any intervention to placebo or active treatment. We included individuals, irrespective of age and sex, diagnosed with MIS, including LM, based on histological examination. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated possible studies for inclusion; extracted data from the included study using a standard data extraction form modified for our review; assessed risk of bias; and analysed data on efficacy, safety, and tolerability. They resolved any disagreements by discussion with a third author. We collected adverse effects information from included studies. MAIN RESULTS: Our search identified only 1 study eligible for inclusion (and 1 ongoing study in active recruitment stage), which was a single centre, open label, parallel group, 2-arm RCT with 90 participants, who had 91 histologically proven LM lesions.Forty-four participants, with 44 LM lesions, were treated with imiquimod 5% cream 5 days per week plus tazarotene 0.1% gel 2 days/week for 3 months, and 46 participants, with 47 LM lesions, were treated with imiquimod 5% cream 5 days per week for 3 months. Two months after cessation of topical treatment, the initial tumour footprint was excised using 2 mm margins via a staged excision. This study was open label, and analysis was not intention-to-treat, leading to a high risk of incomplete outcome data.Our primary outcome 'Histological or clinical complete response' was measured at 5 months in 29/44 participants (66%) treated with imiquimod plus tazarotene (combination therapy) and 27/46 participants (59%) treated with imiquimod (monotherapy). The difference was not statistically significant (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.81 to 1.55, P value = 0.48).With regard to our secondary outcomes on recurrence and inflammation, after a mean follow up of 42 months, no local recurrences were observed among complete responders. Difference in overall inflammation score between the 2 groups was significant (mean difference (MD) 0.6, 95% CI 0.2 to 1, P value = 0.004), with the mean overall inflammation score being significantly higher in the combination group.The study authors did not clearly report on side-effects. Because of adverse effects, there was a dropout rate of 6/44 participants (13.7%) in the combination group compared with 1/46 (2.2%) in the imiquimod monotherapy group (due to excessive inflammation) before the cessation of topical treatment (first 3 months), but this was not statistically significant (RR 6.27, 95% CI 0.79 to 50.02, P value = 0.08). AUTHORS' CONCLUSIONS: There is a lack of high-quality evidence for the treatment of MIS and LM.For the treatment of MIS, we found no RCTs of surgical interventions aiming to optimise margin control (square method, perimeter technique, 'slow Mohs', staged radial sections, staged "mapped" excisions, or Mohs micrographic surgery), which are the most widely used interventions recommended as first-line therapy. The use of non-surgical interventions in selected cases (patients with contraindications to surgical interventions) may be effective and may be considered preferable for experienced providers and under close and adequate follow up.For the treatment of LM, we found no RCTs of surgical interventions, which remain the most widely used and recommended available treatment. The use of non-surgical interventions, such as imiquimod, as monotherapy may be effective and may be considered in selected cases where surgical procedures are contraindicated and used preferentially by experienced providers under close and adequate follow up. The use of topical therapies, such as 5-fluorouracil and imiquimod, as neoadjuvant therapies warrants further investigation. There is insufficient evidence to support or refute the addition of tazarotene to imiquimod as adjuvant therapy; the current evidence suggests that it can increase topical inflammatory response and withdrawal of participants because of treatment-related side-effects.

An evidence-based review of risk-reductive strategies for osteonecrosis of the jaws among cancer patients.

PURPOSE: Bone antiresorptive treatment is associated with osteonecrosis of the jaws. Interventions used to treat this complication are diverse, controversial, and largely empirical but certain risk factors could help in its avoidance. The aim of this evidence-based review is to elucidate any interventions that are effective in reducing the risk for development of ONJ in cancer patients receiving bone antiresorptive therapy and to quantify the effectiveness of such interventions. MATERIALS & METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other trial registries through January 2012. We selected randomized controlled trials (RCTs). Cohort studies were included only as long as there are no RCTs on the same modality. RESULTS: Twelve studies were included in the systematic review while nine studies contributed to the various comparisons. Prescribing denosumab (DSB) instead of zoledronic acid (ZA) may not be expected to reduce risk ONJ (RR:0.71 [99% CI: 0.41-1.24], I2=0%). Prescribing clodronate (RR:10.15 [99% CI: 2.43-42.35], I2=0%) or pamidronate (RR:4.41 [99% CI: 1.90-10.24], I2=16%) instead of ZA may reduce risk for ONJ. Dental extractions remain the most potent risk factor for ONJ (RR:14.04, [99% CI: 10.36-19.03], I2=0%) and their avoidance can be considered an effective risk-reductive intervention. ONJ risk can be reduced by dental prophylactic measures (RR:0.45, [99% CI: 0.23-0.85], I2=7%). CONCLUSIONS: DSB and ZA might cause ONJ more frequently compared with chlodornate or pamidronate. Prescription pamidronate and clodronate helps avoid the complication. Reducing the administered dose for denosumab and zoledronic acid might reduce risk for ONJ as well. More randomized clinical trials comparing reduced doses of these regimens against those currently approved are needed.

Effect of non-steroidal anti-inflammatory drugs on bone turnover: an evidence-based review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for acute and chronic pain control and treatment of inflammation, osteoarthritis and rheumatoid arthritis. NSAIDs have been shown to inhibit bone healing in animal studies due to the inhibition of prostaglandin synthesis. However, little evidence exists regarding the effect of NSAID exposure on human bone metabolism. This systematic review summarizes the current literature of randomized controlled trials (RCTs) investigating NSAIDs with bone remodeling-related outcomes in humans. After performing computerized searches in the most widely indexed databases, study selection, data abstraction and risk of bias assessment were conducted in duplicate. The results were controversial regarding the association of NSAID with bone formation or resorption. Increased bone mineral density following NSAID exposure was reported by some studies. Based on the levels of biochemical markers, no effect was seen on bone formation, while some evidence was found for a decreased rate of bone resorption in NSAID patients. Trials investigating the effects of NSAID treatment on bone metabolism outcomes of human patients are limited. Further research is required to confirm or refute the findings of this systematic review.

Photoletter to the editor: Dermoscopy of granuloma faciale.

Granuloma faciale (GF) is a rare benign inflammatory dermatosis that usually develops as a solitary brownish-red plaque on the face. It clinically mimics and is often misinterpreted as, sarcoidosis, lupus erythematosus, lupus vulgaris, lymphoma or basal cell carcinoma.Dermoscopy, which is valuable for evaluation and differentiation between malignant and benign skin tumors, allows better visualization of dermal vascular structures and color variations. In this context, it might serve as an adjuvant diagnostic tool in the differentiation of inflammatory disorders, too. In the current manuscript, we present the dermoscopic features observed in a lesion of GF and discuss them in correlation with the underlying histopathological alterations.

Novel antimicrobial agents for the management of maxillofacial and neck infections.

BACKGROUND: Maxillofacial and head & neck infections often jeopardize patients' lives. Regional intracranial spread to the cavernous sinus, but also to the mediastinum is common for those left untreated. The divergence of the upper peptic and respiratory tracts from the pharynx, the presence of the brain vasculature, the fine sensory instruments for vision, hearing and taste-smell, and the unique feature of mucosa directly attached to facial bones in the paranasal sinuses, oral cavity and external auditory meatus make this region the most exposed to infections in the human body. Special immune mechanisms have evolved in this area, however infections are still very common. METHODS & RESULTS: We review the unique pathophysiological features of maxillofacial and head & neck infections. We describe novel investigational anti-infective agents, and analyze their potential clinical utility with regard to mechanisms of action and site preference. DISCUSSION: We emphasize on the need for more antimicrobial drug research and discuss on the current skews in pharmaceutical research and manufacturing practices that make new categories of antimicrobial drugs an exceptional entity. Drug patents may need to be expanded both longitudinally in terms of time period but also squarely, potentially including the drug class in the patent rather than the drug itself. Clinicians need to be aware of these limitations and prescribe antibiotics to their patients with parsimony.

New pharmaceutical concepts for sebaceous gland diseases: implementing today's pre-clinical data into tomorrow's daily clinical practice.

The human sebaceous gland is a microscopic branched type multiacinar gland been present everywhere on the body except on the palms and soles, whereas they are sparsely located on the dorsum of hands and feet. Several medical conditions are related with sebaceous gland pathology, such as acne, sebaceous hyperplasia, sebaceous adenoma and sebaceous carcinoma. Acne is a common, complex, chronic disorder of the human pilosebaceous unit that mostly occurs in adolescence and young adulthood. The sebaceous gland plays an exquisite role in the initiation of the disease. The multifactorial nature of the pathogenesis of acne includes increased sebum production, alteration of the quality of sebum lipids, inflammatory processes, interaction with neuropeptides and dysregulation of the hormone microenvironment, follicular hyperkeratinization and inflammation maintained by Propionbacterium acnes products within the follicle. On the other hand, the sebaceous gland, as a major and critical compartment of human skin, is also affected through ageing, both intrinsic and extrinsic, which lead to distinct clinical and histological changes. Intrinsic ageing of the sebaceous gland is determined primarily by genetic factors and hormonal status, with androgens playing a major role. A clinical manifestation associated with intrinsic ageing changes is skin xerosis. Extrinsic ageing of human sebaceous gland is mainly caused by accumulating UV irradiation, especially UVA. Photoageing of sebaceous gland is expressed with a wide spectrum of benign and malignant sebaceous tumours, such as sebaceous hyperplasia, sebaceous carcinoma and Muir-Torre syndrome. This review will focus on the pathogenesis of the most common sebaceous gland diseases and their molecular pathways which may represent future pharmaceutical targets.