Pityriasis rubra pilaris: treatment with biologics - a new promising therapy?

Pityriasis rubra pilaris (PRP) includes a spectrum of rare chronic inflammatory disorders with papulosquamous eruptions of unknown cause. Different etiologies have been proposed such as vitamin A metabolism dysfunction, association with autoimmune disorders, infection or malignancies. However, PRP seems to be a polygenic skin disorder. Classical systemic treatment is empirical and includes retinoids and methotrexate; however, only few series on treatments exist. Recently there has been an increasing number of reports documenting that new biologicals and in particular TNF-α blockers are safe and effective.     

Clinical features and treatments of transient acantholytic dermatosis (Grover’s disease): a systematic review

Grover's disease (GD) is an itchy acantholytic disorder occurring on the trunk of middle‐aged men. Based on the best evidence, this study aimed to provide a summary of the clinical characteristics, disease course and treatments of GD. A systematic review was performed according to PRISMA guidelines for original articles published between 01.01.1970–08.15.2019, assessing clinical features and/or any type of intervention for GD. A total of 263 articles were retrieved, and 116 original reports that were deemed relevant and satisfied the inclusion criteria were included in the analysis (88 case reports, 26 case series and two retrospective reviews). From these articles, 317 patients were identified, with a male‐to‐female ratio of 3.95. The mean age was 59 years (range 11–92). Typical lesions were itchy papules and vesicle‐papules, generally located on the trunk. Spontaneous resolution within one week to eight months was described in 42 % of cases. Topical corticosteroids (TCSs) were the most frequent treatment (response rate of 70 %) followed by systemic retinoids and corticosteroids with response rates of 86 % and 64 %, respectively. According to the results of this review, TCS appears to be the most frequently employed treatment, and we suggest TCS as first‐line therapy. Second‐line treatments could include systemic retinoids or systemic corticosteroids.     

Pityriasis rubra pilaris in children

BACKGROUND: Pityriasis rubra pilaris (PRP) is an uncommon dermatosis in children. Few long-term studies on the treatment and prognosis of PRP in children have been performed. OBJECTIVE: Our purpose was to retrospectively review the clinical course and treatment of all cases of PRP in children 19 years or younger who were seen at the Mayo Clinic. METHODS: The clinical courses of the 30 patients with PRP seen at the Mayo Clinic between 1975 and 1997 were reviewed. RESULTS: The most common presenting form of PRP in children is the type III juvenile form (Griffiths' criteria). Treatment ranged from topical steroids, tar, and ultraviolet B to systemic retinoids and methotrexate. The best response was obtained with isotretinoin; 5 of 6 patients showed 90% to 100% clearing within 6 months of treatment. Follow-up information was obtained by questionnaire and was available for 83% of patients. Overall, 43% had 90% to 100% resolution of their disease, 23% had a moderate response (30%-90% improvement), and 17% had a poor response (<30% improvement). One patient reported spontaneous resolution. Seventeen percent of those who had total clearing had recurrence of PRP within 1 year. CONCLUSION: PRP in children is a noninherited dermatosis with no sex predilection, occurring mainly in the type III classic juvenile form. Retinoids should be considered as first-line treatment for PRP. Recurrence rate, previously thought to be rare, was about 17% in our population.     

An expert view on the treatment of acne with systemic antibiotics and/or oral isotretinoin in the light of the new European recommendations

In 2003 the European Agency for the Evaluation of Medicinal Products amended the summary product characteristics for oral isotretinoin to standardise information provided from the different countries of the European Community. The Committee for Proprietary Medicinal Products recommended that among others, exclusively severe forms of acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to "adequate courses" of standard therapy with systemic antibacterials and local therapy should benefit from oral isotretinoin. However, no indication was provided on what were considered adequate courses or the possibility given to use oral isotretinoin as first line treatment. The aims of the present report were: 1) to provide a specialist view on when it is appropriate to introduce oral isotretinoin as a second line therapy for acne, taking into consideration optimum dosage and duration of systemic antibiotics prior to the start of the oral isotretinoin, and 2) to support the use of oral isotretinoin as first line therapy in specific cases for acne in clinical practice. The recommendations are based on an exhaustive literature review as well as on the personal experience of the members of an European panel of acne specialists. The EEP agreed with the decision made by the CPMP that oral isotretinoin should be administered as 2nd line therapy in those cases of severe acne, which were resistant to or which did not respond successfully to an initial combination regimen with systemic antibiotics and topical treatments (topical retinoids +/- benzoyl peroxide). However, the members emphasized that a number of prognostic factors, as well as psychosocial morbidity should be taken into account when choosing the regimen and that these factors may influence the use of oral isotretinoin as first line therapy.     

Topical retinoids in acne – an evidence‐based overview

Topical retinoids are important tools in the management of acne because they act against comedones and microcomedones and have direct anti‐inflammatory effects. The substances approved for acne treatment comprise tretinoin (all‐trans‐retinoic acid),isotretinoin (13‐cis retinoic acid) as well as the synthetic third‐generation polyaromatic retinoids adapalene and tazarotene,the latter being approved for acne treatment in the US only.Retinaldehyde is used in cosmetic preparations against acne. All topical retinoids are effective as single agents in mild to moderate acne but differ in efficacy and tolerability. Tazarotene 0.1% is more effective than tretinoin 0.025% or 0.1% microsphere gel or adapalene 0.1% gel or cream (EBM‐level 2c). Adapalene 0.1% is equally effective to tretinoin 0.025% or tretinoin microsphere 0.1% gel or tretinoin 0.05% cream or isotretinoin 0.05% gel (EBM‐level 2c). Adapalene 0.1% gel is significantly better tolerated than tazarotene 0.1% gel, tretinoin 0.025% and tretinoin 0.05% gel, tretinoin 0.05% cream,tretinoin microsphere 0.1% gel or isotretinoin 0.05% gel (EBM‐level 2c).The safety profile of topical retinoids differs from their systemic counterparts and is related mainly to local adverse effects, such as erythema, dry‐ness,itching and stinging.The currently available evidence justifies the use of topical retinoids in most types of acne and during maintenance treatment.     

Newer Approaches to the Treatment of Acne Vulgaris

The multifactorial etiology of acne vulgaris makes it challenging to treat. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, azelaic acid, and systemic isotretinoin. Adjunctive and/or emerging approaches include topical dapsone, taurine bromamine, resveratrol, chemical peels, optical treatments, as well as complementary and alternative medications. The purpose of this paper is to discuss the therapies available for acne and their latest developments, including new treatment strategies (i.e. re-evaluation of the use of oral antibiotics and avoidance of topical antibiotic monotherapy, use of subantimicrobial antibiotic dosing, use of low-dose isotretinoin, optical treatments), new formulations (microsponges, liposomes, nanoemulsions, aerosol foams), new combinations (fixed-combination products of topical retinoids and topical antibiotics [essentially clindamycin] or benzoyl peroxide), new agents (topical dapsone, taurine bromamine, resveratrol) and their rationale and likely place in treatment. Acne vaccines, topical natural antimicrobial peptides, and lauric acid represent other promising therapies.     

Systemic therapy with immunosuppressive agents and retinoids in hidradenitis suppurativa: a systematic review

Hidradenitis suppurativa (HS) is a difficult disease to treat. Although the pathogenesis of this inflammatory skin disease is largely unknown, the important role of the immune system has been demonstrated in both experimental and clinical studies. Clinicians are therefore increasingly prescribing systemic treatments with immunosuppressive agents, but the more traditionally used systemic retinoids, especially isotretinoin, also remain relatively common therapies. In order to provide an overview of all currently available systemic immunosuppressive agents and retinoids for the treatment of HS, a systematic search was performed using the Medline and Embase databases. All published papers concerning systemic retinoids or immunosuppressive treatments for HS in adults were included. The primary endpoints were the percentages of significant responders, moderate responders and nonresponders. Other endpoints were the relapse rate and adverse events. In total 87 papers were included, comprising 518 patients with HS who were treated with systemic retinoids, biological agents or another immunosuppressive agents, including colchicine, ciclosporin, dapsone or methotrexate. The highest response rates were observed with infliximab, adalimumab and acitretin. Overall, the quality of evidence was low and differed between the agents, making direct comparisons difficult. However, based on the amount of evidence, infliximab and adalimumab were the most effective agents. Acitretin was also effective in HS, although the quality of the evidence was low. The therapeutic effect of isotretinoin is questionable. Randomized controlled trials are needed to confirm the effectiveness of acitretin, and to identify the most effective immunosuppressive agents in HS.     

Isotretinoin-induced sacroiliitis: Case series of four patients and a systematic review of the literature

Isotretinoin is the mainstay treatment in severe acne; however, its musculoskeletal adverse effects such as lower-back pain can be disabling. Herein, we present four cases of isotretinoin-induced sacroiliitis with variable severity. We also present a review of the literature of isotretinoin-induced sacroiliitis. All our cases were male and human leukocyte antigen (HLA)-B27 negative. Sacroiliitis was detected a median of 55 (10-120) days after isotretinoin initiation. Two patients were responsive to baseline sulfasalazine and indomethacin treatment, while the other two patients required more intensive treatments: adalimumab in one and methotrexate in the other. We also identified 15 articles describing 33 patients (17 of whom were female) with isotretinoin-induced sacroiliitis. Most of them were responsive to low-to-medium doses of systemic steroids or non-steroidal anti-inflammatory drugs (NSAIDs). Our patients illustrate that severity of isotretinoin-induced sacroiliitis varies from patient to patient.     

Effects of isotretinoin on glucose metabolism in patients with acne: A systematic review and meta‐analysis

Previous studies reporting the influence of isotretinoin treatment on glucose metabolism have produced conflicting results. We therefore aimed to examine the effects of isotretinoin treatment on changes in insulin resistance and serum levels of adiponectin in patients with acne. A systematic review and meta‐analysis of the literature published from the inception of isotretinoin to March 31, 2019 were conducted. In the absence of controlled trials, open‐label studies on acne patients receiving isotretinoin treatment were included. Twelve studies met the inclusion criteria. The outcomes included changes in the homeostasis model assessment for insulin resistance (HOMA‐IR) values and serum levels of adiponectin after isotretinoin treatment. Pooled analysis showed that HOMA‐IR values did not change significantly after isotretinoin treatment (standardized mean difference [SMD] = 0.183; 95 % confidence interval [CI] = ?0.004–0.371; I² = 38.3), whereas the level of adiponectin significantly increased (SMD = 0.512; 95 % CI = 0.327–0.698; I² = 10.7). Our study concluded that isotretinoin treatment for patients with acne resulted in an increased serum level of adiponectin but did not have a substantial impact on the status of insulin resistance.     

Efficacy and safety of systemic treatments for moderate‐to‐severe psoriasis: meta‐analysis of randomized controlled trials

Dermatologists may choose from various conventional and biological systemic agents to treat patients with moderate‐to‐severe psoriasis. We set out to analyse systematically the efficacy and tolerability of approved treatments for moderate‐to‐severe psoriasis. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) investigating the efficacy of systemic treatment approved for moderate‐to‐severe psoriasis. Efficacy was assessed as the proportion of participants with 75% improvement in Psoriasis Area and Severity Index at primary efficacy measurement (week 8–16). Safety was summarized as rates of adverse events and withdrawals. Direct and indirect comparative efficacy was assessed by random effects meta‐analysis of risk differences (RDs). In total, 48 eligible RCTs totalling 16 696 patients (11 178 randomized to biologics, 1888 to conventional treatments) were identified. In placebo‐controlled trials, infliximab was the most efficacious [RD 76%, 95% confidence interval (CI) 73–79%]. Adalimumab (RD 61%, 95% CI 56–67%), and ustekinumab 45 mg (RD 63%, 95% CI 59–66%) and 90 mg (RD 67%, 95% CI 60–74%) each had similar efficacy. These biologics are more effective than etanercept and all conventional treatments. Head‐to‐head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept, the nonsignificant superiority of ciclosporin over MTX, and the dose‐dependent efficacy of etanercept and ustekinumab. Fumaric acid is as efficacious as MTX. Safety of treatments could not be pooled due to a lack of standardization in reporting across trials. In conclusion, the qualitative and quantitative evidence is much stronger for biological interventions than for conventional treatments.     

Remission period in psoriasis after multiple cycles of narrowband ultraviolet B phototherapy

The aim of this study was to investigate the duration of remission periods in psoriasis after narrowband ultraviolet B (NB‐UVB) phototherapy, especially during multiple cycles of treatment. We analyzed 63 patients (101 cases) demonstrating marked improvement after NB‐UVB phototherapy. The remission period was defined as the duration of time from the end of phototherapy until treatment using either phototherapy or systemic treatments was required again. It was found that an age of 60 years or older, history of systemic therapy within 6 months and three or more phototherapy cycles were significantly associated with shorter remission periods. Furthermore, multivariate analysis confirmed that three or more phototherapy cycles (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.73–9.33; P = 0.001) and a history of systemic therapy (OR, 2.2; 95% CI, 1.27–3.95; P = 0.005) were independently associated with the shorter remission period. In conclusion, when planning NB‐UVB phototherapy for psoriatic patients who have undergone multiple phototherapy cycles, clinicians should consider the possibility of shorter remission periods.     

Efficacy and safety of systemic treatments in psoriatic arthritis: a systematic review,meta‐analysis and GRADE evaluation

Twenty per cent of patients with plaque psoriasis also have psoriatic arthritis – a disease affecting joints and entheses. Different treatment options exist but currently no succinct systematic overview exists. A systematic review of approved systemic treatments for psoriatic arthritis was conducted. We systematically searched in three databases (last update September 2017). Data were extracted for ACR20/50, HAQ‐DI, SF‐36 and adverse/serious adverse events after 16–24 weeks. We assessed the quality of evidence using GRADE. Twenty trials were included. Three trials compared two active substances. Results for ACR20 were infliximab + methotrexate vs. methotrexate: RR 1.40 (95% CI 1.07–1.84) very low quality evidence; ixekizumab Q2W vs. adalimumab Q2W: RR 1.08 (95% CI 0.86–1.36) very low quality, leflunomide vs. methotrexate: RR 1.01, (95% CI 0.84–1.21) low quality. Eighteen drug vs. placebo comparisons were included. For ACR20/50, HAQ‐DI and SF‐36, the active treatment was efficacious and the quality of the evidence was mostly moderate to low (15 of 18 comparisons). The quality of evidence for (serious) adverse events was mostly low; differences were rare. In three placebo‐controlled comparisons, leflunomide, MTX and sulfasalazine failed to show statistical superiority for ACR. Besides the established treatment of anti‐TNF antibodies and ustekinumab for psoriatic arthritis, the newer treatment options of IL17 antibodies and apremilast are also effective for the treatment of psoriatic arthritis. Based on just one comparative trial and one drug each, the new class of anti‐IL 17 antibodies appears to be equally effective as the group of anti‐TNF antibodies; for apremilast, this is yet unclear.     

A Systematic Review of Systemic Medications for Pustular Psoriasis in Pediatrics

There is lack of information and evidence‐based studies on the treatment of pediatric pustular psoriasis. Previous reports have emphasized the limitations of the existing data and encouraged the exploration of therapy optimization through more structured research. The objective of the current study was to perform a systematic review of systemic interventions for pediatric pustular psoriasis with an emphasis on clinical response and treatment outcomes. A systematic literature search was conducted using the PubMed and Embase databases from 1982 to 2012. Of 632 references identified, 14 met our inclusion criteria and were included in the analysis. A cohort of eight patients from the Hospital for Sick Children, Toronto, Canada, was also included. Information was limited to systemic treatments in children. Only English‐ and Spanish‐language articles were included. Information was gathered from 24 patients, 22 of whom (92%) presented with generalized pustular psoriasis and 2 (8%) with acral distribution. The mean age at presentation was 6.3 ± 4.9 years. More than one intervention was required in 12 (50%) cases. The most common therapies used for generalized pustular psoriasis were acitretin, cyclosporine, and methotrexate. We identified that there is lack of information regarding long‐term response to systemic drugs because the data were focused on treatment initiation. Treatment of pustular psoriasis in pediatrics is challenging. Although acitretin, methotrexate, and cyclosporine seem to control generalized pustular psoriasis within 3 months of therapy initiation, information on long‐term follow‐up is lacking. Furthermore, physicians may encounter difficulties after discontinuing or tapering medications.     

S2k guideline for treatment of cutaneous lupus erythematosus – guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV)

Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used ‘off‐label’. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first‐line or second‐line topical therapeutic option. Antimalarials are recommended as first‐line and long‐term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first‐line treatment in highly active and/or severe CLE. Second‐ and third‐line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy‐refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B‐cell‐ or interferon α‐targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.     

The negligible systemic availability of retinoids with multiple and excessive topical application of isotretinoin 0.05% gel (Isotrex) in patients with acne vulgaris.

The potential systemic availability of retinoids from topically applied isotretinoin was assessed in 12 men with acne vulgaris. Isotretinoin 0.05% gel was applied to patients at a daily dose of 20 gm (equivalent to 10 mg of isotretinoin) over a 1900 cm2 surface area of skin on the face, back, and chest for 30 days. Blood samples were collected throughout the study and up to 48 hours after the last topical application; they were assayed for isotretinoin, tretinoin, and 4-oxo-isotretinoin by specific high-performance liquid chromatography. Plasma concentrations of isotretinoin, tretinoin, and 4-oxo-isotretinoin were not measurable (less than 20 ng/ml) at any time. Most adverse experiences were cutaneous; a few systemic adverse experiences were judged to be remotely related to topical drug administration. The lack of measurable plasma concentrations of isotretinoin, tretinoin, or 4-oxo-isotretinoin and systemic adverse experiences indicates negligible systemic availability of retinoids even after multiple application of isotretinoin 0.05% gel at doses approximately 12 times greater than normal daily use.     

Management of digital mucous cysts: a systematic review and treatment algorithm

Digital mucous cysts (DMC) are benign, highly recurrent lesions of the digits. To date, there is still no treatment agreement on the treatment of DMC. Herein, we review available data on treatment modalities, including both surgical and nonsurgical techniques, and to provide a practical algorithm for the management of DMC. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane databases. Articles studying the management of DMC were included in this review. A total of 40 articles were included in the review. The five most frequently used treatments for DMC were surgery (n = 849), expression of cyst content (n = 132), sclerotherapy (n = 119), corticosteroid injection (n = 108), and cryotherapy (n = 103). Surgery yielded the highest cure rate among all treatment modalities (95%) compared to sclerotherapy (77%), cryotherapy (72%), corticosteroid injection (61%), and expression of cyst content (39%) (P < 0.001). Surgery should be considered as the first‐line treatment for DMC. Second‐line treatments include sclerotherapy and cryotherapy. Third‐line treatments include corticosteroid injections, expression of cyst content, and less‐studied modalities. Surgery showed the highest cure rates. Future adequately designed randomized controlled trials are warranted to compare different treatment modalities.     

Individualizing treatment and choice of medication in lichen planus: a step by step approach

Although lichen planus is one of the most common dermatological entities, very few reviews on its management exist in the literature. Standard therapeutic approaches include various topical treatments (including topical corticosteroids, calcineurin inhibitors, vitamin D analogs) and phototherapy modalities, as well as systemic corticosteroids and systemic retinoids. While localized skin lesions are easily managed with standard modalities, generalized forms and in particular involvement of hair follicles, nails and mucosa, as well as eyes are often challenging. This review proposes an evidence‐based and differential therapeutic regime, taking into account many new emerging systemic therapies to help clinicians optimize treatment according to the type, extent and severity of the disease. An individual therapeutic ladder has been developed for each location, starting with standard modalities and ranking alternative systemic treatments (mainly methotrexate and hydroxychloroquine, as well as cyclosporine, azathioprine and mycophenolate mofetil) according to efficacy, evidence level and side‐effect profile.     

Ultraviolet B Phototherapy for Psoriasis: Review of Practical Guidelines

Psoriasis is an inflammatory skin condition that affects approximately 2 % of people worldwide. Topical treatments, systemic treatments, biologic agents, and phototherapy are all treatment options for psoriasis. Ultraviolet (UV) B phototherapy is most appropriate for patients with >10 % affected body surface area who have not responded to topical treatments. This review outlines the use, dosage, safety, and efficacy of narrowband UVB (NB-UVB) and targeted phototherapy. NB-UVB and excimer laser are effective treatment options for psoriasis; they are administered two to three times weekly until clearance followed by maintenance treatment before discontinuation. Long-term data on NB-UVB indicate that it has a good safety profile. NB-UVB is commonly used with adjunctive topical treatments such as emollients, calcipotriene, cortico-steroids, retinoids, and tar. NB-UVB can be used in selected patients with traditional systemic agents such as methotrexate, mycophenolate mofetil, and cyclosporine, although the duration of the combined treatment should be kept to a minimum and patients need to be closely monitored. Acitretin can be safely used with phototherapy, but robust data on the combination use of biologic agents or phosphodiesterase inhibitors with phototherapy are lacking.