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Generalized pustular psoriasis (GPP) is a rare and severe subtype of psoriasis. Because of its rarity, GPP studies with a large sample size have been scarce. We studied the characteristics of GPP and pustular psoriasis using data from the West Japan Psoriasis Registry that had been registered until the end of December 2020. The dataset included 104 patients with pustular psoriasis and 1290 patients with other subtypes of psoriasis. Multivariate analysis revealed a significantly greater number of female patients, a significantly lower mean body mass index, and a significantly lower ratio of habitual drinkers in pustular psoriasis, compared to other subtypes of psoriasis. Of the 104 patients, 102 had GPP, including 88 von Zumbusch, 10 juvenile-onset, and four annular pustular psoriasis. Although the male : female ratio of GPP with psoriasis vulgaris (GPP+PsV) (47/20) was similar to that of psoriasis in Japan, the GPP without PsV (GPP-PsV) group highlighted a female predominance (13/22). The mean age at GPP onset was 45.3 years, and the mean interval from PsV onset to GPP onset was 12.5 years. Four of nine patients with GPP had an IL36RN gene mutation. Infection, medicine, and pregnancy were the precipitating factors for GPP. A family history of psoriasis was present in eight (7.8%) patients with GPP. Twenty-four patients with GPP had psoriatic arthritis. Biologics were used in 76.5% of patients with GPP, followed by etretinate (37.3%), cyclosporine (24.5%), methotrexate (13.7%), apremilast (8.8%), and granulocyte and monocyte adsorption apheresis (6.9%). Etretinate was used in 17 (51.5%) of 33 patients with GPP with less than 10-year history. Thus, etretinate remains a good treatment option for GPP even in the era of biologics. Hypertension was the most commonly identified comorbidity, followed by diabetes. We believe that the characteristics revealed in this study can further contribute to effective GPP management.

The efficacy and safety of new psoriatic treatments are confirmed in clinical trials, but such clinical trial data are limited by the number and heterogeneity of patients. Furthermore, the prevalence and characteristics of psoriasis differ among racial groups. Therefore, it is important to obtain real-world evidence in specific regions. To identify the optimal systemic treatment for psoriatic patients in Western Japan, we established the Western Japan Psoriasis Registry (WJPR). This registry is led by a neutral physicians' league associated with university hospitals, general hospitals, and clinics that specialize in treatment of psoriasis. Systemically treated psoriatic patients who provided written informed consent were enrolled, and data were collected on their background information, several patient-reported outcomes, dermatologists' objective evaluations, and treatment regimens. Patient enrollment began in 2019, and 1394 patients had been recruited by the end of 2020. The prevalence of psoriatic arthritis was 27.2% and that of pustular psoriasis was 7.5%. The mean body mass index was 24.1 kg/m2 , and 12% of patients had severe obesity (body mass index ≥30 kg/m2 ). Major comorbidities were hypertension (35.0%), diabetes (14.1%), and hyperlipidemia (12.2%). Serological data showed that hepatitis B virus surface antigen, anti-hepatitis B virus core antibody, anti-hepatitis C virus antibody, and human T-cell leukemia virus type 1 antibody were detected in 1.1%, 18.0%, 3.1%, and 3.7% of patients, respectively. The most frequently used small-molecule-systemic intervention was apremilast (18.0%), followed by methotrexate (7.7%), etretinate (4.2%), and cyclosporin (3.7%). The most frequently used biologics were interleukin (IL)-17 inhibitors (31.8%), followed by IL-23 inhibitors (including IL-12/23 inhibitors) (26.7%), and tumor necrosis factor inhibitors (11.1%). The WJPR is the first Japanese prospective observational cohort of psoriatic patients. Annual WJPR updates may provide the incidences of comorbidities such as cardiovascular events or onset of arthritis in systemically treated patients, identify rare complications, and identify the optimal treatment regimens for various psoriatic patients.

Background: Genital warts, caused by the human papillomavirus, are a common sexually transmitted disease. The warts can regress spontaneously or exhibit a persistent clinical course. Various therapeutic modalities are available, yet none is curative, and there may be recurrences. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for genital warts are limited. Objective: To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of genital warts. Methods: A systematic review and meta-analysis of all publications evaluating topical or systemic retinoids for the treatment of genital warts was performed. The primary outcome was complete response (CR); the secondary outcomes were recurrence rate and adverse events. Results: Six publications were evaluated, three randomized controlled trials and three prospective cohort studies, including a total of 141 patients with genital warts treated exclusively with retinoids (90% with isotretinoin). CR rates were 100% for systemic etretinate (3 out of 3 patients, 95% CI 28–81%) and 56% for isotretinoin (95% CI 28–81%; I2 = 84%). Topical etretinate did not induce CR. The most common side effect of topical agents was irritant contact dermatitis (36%) and that of systemic agents mucocutaneous disorders (80%). The relapse rate was 12% for oral isotretinoin and was unavailable for the other modalities. Conclusions: Current data suggest that unlike topical retinoids, systemic retinoids are an effective and safe treatment for genital warts. Further studies are required to determine their specific role and the most effective regimen for each derivative.

AimTo systematically identify studies of implementing risk management measures when prescribing teratogenic medicines for women of childbearing age and studies reporting risk perceptions of teratogenic medications.MethodsMEDLINE, CINAHL, Scopus, EMBASE, and International Pharmaceutical Abstracts were searched. Studies were included in the risk management section if they reported any of the following risk management measures: teratogenic counseling, contraceptive counseling, pregnancy testing before starting treatment, pregnancy testing during treatment, use of contraception before starting treatment, and use of contraception during treatment. Studies were included in the perceptions section if they reported perceived teratogenic risk as numerical value.ResultsFifty‐five studies were included in the risk management section and seven studies were included in the perceptions sections. Prevalence of risk management measures varied as follows: teratogenic counseling (9.5%–99.3%), contraceptive counseling (6.1%–98%), pregnancy testing before starting treatment (0%–95.1%), pregnancy testing during treatment (12.7%–100%), contraception use before starting treatment (15.7%–94%), and contraception use during treatment (1.7%–100%). A proper estimation of the teratogenic risk was reported for thalidomide (by general practitioners and obstetric/gynecologists), for etretinate (by pregnant women), and for misoprostol (by pregnant and nonpregnant women). An under‐estimation was reported for warfarin and retinoids (by general practitioners and obstetric/gynecologists). And over‐estimation was reported for thalidomide, valproate, lithium, isotretinoin, phenytoin, warfarin and etretinate by different populations.ConclusionConsiderable variation in the implementation of risk management measures when prescribing teratogenic medicines to women of childbearing age is reported in the literature. A common tendency to over‐estimate the risk of teratogenic medications was evident.

Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In this article we review the literature on medication-induced hair repigmentation, discuss the potential mechanisms of action, and review the quality of the literary data. To date, there have been 27 studies discussing medication-induced gray hair repigmentation, including 6 articles on gray hair repigmentation as a primary objective, notably with psoralen treatment or vitamin supplementation, and 21 reports on medication-induced gray hair repigmentation as an incidental finding. Medications noted in the literature include anti-inflammatory medications (thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, cyclosporin, cisplatinum, interferon-α, and psoralen), stimulators of melanogenesis (latanoprost, erlotinib, imatinib, tamoxifen, and levodopa), vitamins (calcium pantothenate and para-amino benzoic acid), a medication that accumulates in tissues (clofazimine), and a medication with an undetermined mechanism (captopril). Diffuse repigmentation of gray hair can be induced by certain medications that inhibit inflammation or stimulate melanogenesis. There is also low-quality evidence that some vitamin B complex supplementation can promote gray hair darkening. While these compounds are not currently indicated for the treatment of gray hair, their mechanisms shed light on targets for future medications for hair repigmentation.

A prospective clinical trial was carried out in a 6-week-old male Jack Russell terrier with congenital ichthyosis to evaluate stratum corneum lipids; transmission electron microscopy of skin specimens; and clinical and dermatopathological response to vitamin A alcohol therapy. Also evaluated were the clinical, dermatopathological, and epidermal cell proliferation kinetics response to a synthetic retinoid in a dog with congenital ichthyosis. Epidermal cell renewal time was markedly decreased compared with normal and seborrhoeic dogs. Skin specimens were characterized by severe and diffuse compact orthokeratosis that extended into the infundi-bulum of the hair follicles. The stratum granulosum was normal. On transmission electron microscopy, the stratum corneum was thickened and intercorneocyte spaces were extremely narrow. The first three corneocyte layers contained tonofilaments that were irregular, coarse and wavy. Tonofilament packing appeared more normal and regular in the fourth and fifth corneocyte layers. Outer layers of stratum corneum were extraordinarily electron-dense compared with normal. There was a decrease in stratum corneum free fatty acid and acyl-ceramide and an increase in ceramide III levels compared with three normal dogs. Three months of oral vitamin A alcohol did not result in clinical improvement, although histologically the orthokeratosis was less compact. After 6 months of oral etretinate therapy, comedones and scales were markedly less evident grossly. Although compact orthokeratosis was still present on histological examination of skin, it was less than that present at 6 weeks of age. Epidermal cell kinetics were not altered after etretinate therapy.

Acitretin, an active metabolite of etretinate, is the most widely used systemic retinoid in the treatment of psoriasis. Several side effects of acitretin have been reported such as teratogenicity, cheilitis, xerosis, dyslipidemia, and photosensitivity. Here, we reported a case of acitretin-induced intermittent asymptomatic fever in a 79-year-old male psoriasis patient. To the best of our knowledge, only one such case has been reported in the literature so far. We report our case to draw clinical attention that acitretin may cause drug fever, which might not be a rare phenomenon.

Since the US Food and Drug Administration (FDA) approved tretinoin in 1971, retinoids alone or combined with other agents have become the mainstay of acne treatment. Retinoids act through binding to retinoic acid receptors, altering expression levels of hundreds of cellular proteins affecting multiple pathways involved in acne pathogenesis. Retinoids have evolved from first-generation agents, such as tretinoin, through chemical modifications resulting in a second generation (etretinate and acitretin for psoriasis), a third generation (adapalene and tazarotene) and, most recently, a fourth (trifarotene). For all topical retinoids, local irritation has been associated with poor tolerability and suboptimal adherence. Efforts to improve tolerability have utilized novel delivery systems and/or novel agents. This qualitative literature review summarizes the evolution of the four topical single-agent retinoids available for the treatment of acne in the US today and their various formulations, presenting the rationale behind their development and data from key studies.

A 56-year-old woman had noticed the erosion of oral mucosa and tongue 8 years ago. The mucosal lesions had been initially diagnosed as oral lichen planus and resistant to various treatments with prednisolone, etretinate and mizoribine and so on. One year ago, rapidly growing verrucous lesion occurred on her upper lip. Although we administered intralesional radiation therapy, the tumor recurred and new whitish lesions on the buccal mucosa and hard palate occurred 9 months after treatment. We confirmed an anatomical blood supply to the tumors by a fluorescent real-time imaging system and subsequently administered the intra-arterial infusion of peplomycin through retrograde catheters from bilateral superficial temporal arteries under the final diagnosis as oral florid papillomatosis (OFP). The tumors were dramatically shrunk and did not recur 16 months after treatment. OFP is known as clinically multiple whitish and verrucous lesions over the oral cavity and lip and a subtype of SCC with high differentiation. We suppose that an intra-arterial infusion therapy of peplomycin should be considered as the curative treatment for OFP.

Mal de Meleda (MdM) is an autosomal recessive form of palmoplantar keratoderma, that is characterized by transgradient keratoderma with associated scleroatrophy, nail changes, pseudoainhum around digits and perioral erythema, without a tendency for spontaneous resolution. Mal de Meleda can lead to severe flexion contractures in some patients as well as mycotic over-rinfections with significant impact on quality of life and daily activity. Mal de Meleda is a rare genetic disorder but no standardized treatment has been established. Treatment options for this disease include topical keratolytic agents, propylene glycol, topical 5-fluorouracil and surgical treatment. In addition, it has been reported that etretinate and acitretin, usually produce improvement. Herein, we present a case of Mal de Meleda with lips involvement which showed significant clinical improvement with acitritin.

Cutaneous-type adult T-cell leukemia-lymphoma is treated with antiviral or skin-directed therapy. Medications that are used to treat skin lesions of cutaneous T-cell lymphomas are also used for the cutaneous-type adult T-cell leukemia-lymphoma. Etretinate, a synthetic retinoid, has been used for treating cutaneous T-cell lymphomas; however, its clinical effectiveness for the treatment of cutaneous-type adult T-cell leukemia-lymphoma has not been fully studied. We conducted a retrospective assessment of the efficacy and safety of etretinate in 9 patients with cutaneous-type adult T-cell leukemia-lymphoma. Complete and partial responses to etretinate were observed in 1 and 7 patients, respectively. Among the responders, remission was maintained for more than 6 years in 2 patients. These results suggest that etretinate is a promising treatment option for cutaneous-type adult T-cell leukemia-lymphoma.

Electron beam therapy (EBT) is an established treatment for mycosis fungoides (MF), but evidence for the use of EBT in advanced cutaneous conditions is limited, and optimal scheduling of the regimen for such conditions remains unclear. We report the case of a 44-year-old woman diagnosed with MF with widespread cutaneous lesions, including multiple huge tumours in the craniofacial area. Low-dose total skin (TS)EBT and subsequent localized skin (LS)EBT achieved striking improvements in eruptions. Oral etretinate was also administered during therapy. Our experience implies that combined TSEBT and LSEBT may be worth attempting when a patient presents with both widespread lesions and prominent tumours, even when the tumours are extremely large.

Since 1982, the Japanese Society for Psoriasis Research has conducted annual epidemiological surveys of patients with psoriasis. Kawada et al. have reported data for 1982-2001 and Takahashi et al. have reported data for 2002-2008. The present study evaluated 9290 psoriatic cases according to age and sex (2009-2012). The male : female ratio was 2.08:1 (6281 male patients [67.6%] to 3009 female patients [32.4%]). The most prevalent type was psoriasis vulgaris (85.6% of all cases), which was followed by psoriasis arthropathica (6.0%), psoriasis guttate acuta (3.2%), Zumbusch-type generalized pustular psoriasis (1.8%) and psoriasis erythroderma (1.5%). Psoriasis vulgaris was the most prevalent type for all ages, while psoriasis arthropathica and psoriasis guttate acuta were most prevalent among patients aged less than 65 years. The present survey detected an increased number of cases with comorbid diabetes and/or arthritis symptoms compared with the previous surveys. We found that treatments frequently involved topical corticosteroids (89.7% of cases) and vitamin D3 ointments (78.0% of cases), with a notable increase in the use of vitamin D3 ointments. Systemic treatments were used in 33.3% of cases, including cyclosporin (33.6%), etretinate (19.5%), methotrexate (8.6%), infliximab (11.4%), adalimumab (10.9%) and ustekinumab (6.2%). Phototherapy was used in 30.9% of cases. Although psoralen plus ultraviolet A therapy was the predominant phototherapy during previous studies, the present survey revealed that narrowband ultraviolet B therapy was used in 84.5% of phototherapy-treated cases. Thus, the present survey revealed major changes in treatment trends.

A local epidemiological survey of psoriasis was conducted from 19 February to 30 June 2016 in Matsumoto city, Nagano Prefecture, Japan. Patients were predominantly male (268 cases, 71.5% males vs 107 cases, 28.5% females). We estimated that the prevalence of psoriasis was 0.097% in the Matsumoto area. The clinical types of psoriasis identified were psoriasis vulgaris (90.7%), psoriatic arthritis (5.9%), pustular psoriasis (2.1%), guttate psoriasis (1.0%) and psoriatic erythroderma (0.3%). The topical therapeutic agents included corticosteroids (84.0%), vitamin D3 analogs (61.5%), and a combination of calcipotriol and betamethasone dipropionate (31.0%). Current systemic treatments included cyclosporin (9.0%), etretinate (7.4%) and methotrexate (1.3%). Biologic treatments included adalimumab (4.0%), ustekinumab (2.7%), infliximab (1.3%) and secukinumab (0.8%). Ultraviolet B therapy (11.3%) was the predominant phototherapy in which narrow band ultraviolet B therapy accounted for the majority, followed by psoralen and ultraviolet A therapy (1.0%). According to the recent evolution of psoriasis treatment, the use of biologics has been increasing. This study demonstrates the changes of treatment trends of psoriasis in a non-metropolitan regional area.

Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement. Lichen amyloidosis, macular amyloidosis, and (primary localized cutaneous) nodular amyloidosis are different subtypes of PLCA. The aim of this study was to review the current reported treatment options for PLCA. This systematic review was based on a search in the PubMed database for English and German articles from 1985 to 2016. Reports on the treatment of PLCA were limited predominantly to case reports or small case series. There were a few clinical trials but these lacked control groups. A variety of treatment options for PLCA were reported including retinoids, corticosteroids, cyclophosphamide, cyclosporine, amitriptyline, colchicine, cepharanthin, tacrolimus, dimethyl sulfoxide, vitamin D3 analogs, capsaicin, menthol, hydrocolloid dressings, surgical modalities, laser treatment, and phototherapy. No definitive recommendation of preferable treatment procedures can be made based on the analyzed literature. Randomized controlled trials are needed to offer patients an evidence-based therapy with high-quality standardized treatment regimens for PLCA.

Familial benign chronic pemphigus or Hailey-Hailey disease (HHD) is an autosomal dominant genodermatosis with complete penetrance that was initially described by dermatologists and brothers Howard and Hugh Hailey.1 This disorder results from mutations in the ATP2C1 gene on chromosome 3q21, which encodes the Golgi-associated Ca2+ ATPase. Mutations in this gene lead to abnormal intracellular Ca2+ signaling leading to impaired processing of junctional proteins needed for cell-cell adhesion. The generalized or disseminated form of HHD is rarely documented, but appears to typically be induced by microbial colonization and secondary infections. In particular, Staphylococcal infection can potentiate acantholysis and may lead to severe widespread blistering.2, 3, 4, 5 Other articles suggest that the generalized condition can be triggered by a Koebner-like reaction or even sensitivity to nonsteroidal anti-inflammatory drugs.3 Treatment for generalized HHD varies.2, 3, 4, 5 Oral corticosteroids are most commonly recommended for treatment; however, alternative interventions include oral retinoids, including etretinate,4 cyclosporine, methotrexate, dapsone, and topical tacrolimus.3 In nongeneralized HHD, there are a few published case reports of HHD treated successfully with low-dose naltrexone (LDN).6, 7, 8, 9

A 60-year-old man was diagnosed with psoriasis 4 years ago. Treatment with adalimumab (a monoclonal anti-TNF-α antibody) became ineffective 1 year ago, and proteinuria and urinary occult blood were detected. Treatment with topical medicine, ultraviolet therapy, and etretinate resulted in remission of psoriasis, and proteinuria and hematuria also improved. For maintenance of remission, treatment with secukinumab (a human anti-interleukin-17A monoclonal antibody) was initiated. After the induction phase, treatment was changed from once a week to once every 4 weeks. After 5 months, he developed nephritis with kidney dysfunction, hematuria, and severe proteinuria (14 g/g Cr) accompanied by pitting edema. After admission, treatment with secukinumab was continued. Kidney biopsy revealed IgA nephropathy with fibrocellular crescents, and immunofluorescence analysis did not detect galactose-deficient IgA1. With these findings, he was diagnosed as secondary IgA nephropathy associated with psoriasis. Tonsillectomy followed by steroid pulse therapy prevented proteinuria and kidney function. In this case, treatment of refractory psoriasis with secukinumab and tonsillectomy was effective, leading to remission of relapsing secondary IgA nephropathy. Therefore, secukinumab might play an immunological role in the treatment of nephropathy.

A 67-year-old man, who had been diagnosed with psoriasis 30 years prior, visited our hospital with a complaint of verrucous nodules in the lower legs, which had developed 15 years previously. We diagnosed him as having psoriasis verrucosa of the legs and plaque psoriasis of the torso. Because the lesions were resistant to topical glucocorticoids and vitamin D3 , a verrucous lesion in the right leg was treated with surgical ablation, which resulted in the development of generalized pustular psoriasis. After pustular lesions were cleared by systemic glucocorticoids and methotrexate, we treated him with etretinate and cyclosporin, but the verrucous lesions accompanied by chronic bacterial infection persisted over time. One year ago, treatment with recently-approved apremilast was started. It immediately attenuated the plaques and erythropapular lesions of the trunk. Surprisingly, the verrucous nodules of both legs showed reduction in size in 2 months.

Papillon–Lefevre (PLS) is a rare autosomal recessive disorder of keratinization characterized by symmetric, trans-gradient type palmoplantar keratoderma (PPK), rapidly progressive periodontopathy, and precocious loss of dentition. The management of this condition is difficult and needs a combined approach of both dermatologist and periodontologist. Different treatment options tried previously include keratolytic agents such as salicylic acid, urea, topical steroids in combination with keratolytic, propylene glycol, and systemic retinoids such as etretinate, isotretinoin, and acitretin. Both skin and dental manifestations show good therapeutic responses to systemic retinoids. Thereby, we report a case of PLS in a young female child who showed an excellent response to oral acitretin therapy.

Psoriasis is a prevalent cutaneous condition with severe physical and psychological manifestations. Since the advent of biologics, clinical outcomes in psoriasis have improved. However, retinoids are useful in the correct clinical context. Tazarotene and acitretin are currently the only US Food and Drug Administration approved retinoids for treatment of psoriasis. Both topical tazarotene and oral acitretin act on retinoic acid receptors and retinoid-X-receptors, resulting in altered gene expression of inflammatory cytokines and inhibition of keratinocyte proliferation. Areas covered: This article provides an in-depth pharmacologic and clinical review on the use of tazarotene and acitretin in psoriasis. The PubMed database was searched using combinations of keywords: acitretin, bioavailability, dosing, efficacy, etretinate, interactions, mechanism, pharmacodynamics, pharmacokinetics, pharmacogenetics, psoriasis, safety, tazarotene, tolerability, and toxicity. Expert opinion: Tazarotene and acitretin are effective treatments for psoriasis. Benefits include lack of immunosuppression and success treating inflammatory psoriasis. When combined with other topical and systemic agents, both retinoids improve clinical efficacy while lowering the treatment threshold. However, topical adherence and bothersome side effects can limit retinoid use. Acitretin and tazarotene both improve outcomes through a unique mechanism that especially benefits subsets of patients, despite side effects and limitations.

Apremilast is a novel oral phosphodiesterase 4 inhibitor effective for psoriasis. It regulates the production of pro-inflammatory mediators. Apremilast was approved in December 2016 in Japan; however, its efficacy and safety in a real-world setting among Japanese patients have not been reported. We report on 44 patients treated with apremilast between March and October 2017. The median treatment duration was 25 weeks (range, 2-33). Thirty-five patients (79.5%) continued the drug for at least 23 weeks, and five (11.4%) achieved a Psoriasis Area and Severity Index 100 response within 12 weeks. Nine patients discontinued the drug within 24 weeks mainly due to insufficient efficacy (n = 3) and adverse events (n = 4). Seven patients continued their previous systemic therapies such as cyclosporin (n = 1), methotrexate (n = 1), etretinate + methotrexate (n = 1) and biologics (n = 4) combined with apremilast. Of these patients, 55.9% had at least one adverse event although no severe adverse events. The most common adverse event was diarrhea (31.8%), followed by nausea (25.0%), headache (13.6%), abdominal discomfort (6.8%) and vomiting (6.8%). The proportion of diarrhea in our patients was higher than those of previous clinical trials. Among 10 patients with psoriatic arthritis, apremilast did not improve joint pain in nine (90%). To investigate the relationship between treatment efficacy and plaque size, we defined a small plaque as an individual rash diameter of 1 inch or less. The efficacy of apremilast was greater in patients with small plaques than in patients with large plaques.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous disorder. Treatment is challenging; the armamentarium consists of topical corticosteroids, phototherapy, classic systemic treatments such as retinoids or immunosuppressive drugs, and most recently biologicals. However, the relative effectiveness of therapies is unclear. Our objective was to review the published literature on systemic treatment of PRP. A systematic review was conducted on PubMed and the Cochrane Library up to 5 September 2017. Studies evaluating any systemic treatments of PRP (except for historical treatments) were included. Overall, 182 studies met the predefined inclusion criteria, and reported on 475 patients and 652 courses of treatment. 42.0 % (225/514) of all patients treated with retinoids achieved an excellent response (isotretinoin: 61.1 % [102/167], etretinate: 47 % [54/115], and acitretin: 24.7 % [43/174]) compared to an excellent response rate of 33.1 % (53/160) with methotrexate. Therapy with biologicals was successful in 51.0 % of patients (71/133) (ustekinumab: 62.5 % [10/16], infliximab: 57.1 % [28/49], etanercept: 53.3 % [16/30], and adalimumab: 46.4 % [13/28]). This review balances effectiveness, side effects, experience, and drug costs in order to suggest a treatment regimen starting with isotretinoin as first-line, methotrexate as second-line and biologicals as third-line treatment for this difficult-to-treat dermatosis.

Vemurafenib, a kinase inhibitor that targets tumors with the BRAF V600E mutation, is a promising option for unresectable or metastatic melanoma. Cutaneous side-effects have been reported including alopecia, photosensitivity, squamous cell carcinoma, keratoacanthomas, keratosis pilaris-like eruption, and palmoplantar hyperkeratosis. Acneiform eruptions have been reported in 3%-6% of the patients treated with BRAF inhibitors,and 5 cases are described in the literature. Although they responded well to topical therapies, oral antibiotics, or observation, one case required oral etretinate and the withdrawal of vemurafenib because the adverse event reached grade 3. We report one case of a severe acneiform eruption associated with vemurafenib with a good response to isotretinoin allowing continuation of the BRAF inhibitor.

Punctate palmoplantar keratoderma type 1 (PPKP1) is a rare autosomal dominant disorder of keratinization, clinically characterized by punctate keratotic papules affecting the palmoplantar skin. Loss-of-function mutations in AAGAB have recently been reported as a cause of PPKP1. Despite the discovery of the genetic cause of PPKP1, pathogenesis-based therapies are still unavailable. Moreover, little is known about the effectiveness of treatments for PPKP1. In this study, we analyzed a Japanese woman with PPKP1 and identified a novel frame-shift mutation c.195_198del4 (p.Lys66Phefs*43) in AAGAB. Moreover, low-dose etretinate was effective in improving the PPKP1 lesions in our patient. Our published work review identified only eight cases of PPKP1 with successful response to topical or systemic treatments. Notably, six of the cases were successfully treated with systemic retinoids. Thus, this study clearly provides further evidence that PPKP1 is caused by AAGAB mutations and that systemic retinoids are the most promising current treatment for PPKP1.

A 78-year-old woman who had been suffering from psoriasis vulgaris for 31 years was admitted to hospital because of her erythroderma. A toxic eruption was suspected and she was treated with prednisolone 30 mg daily. However, it was ineffective and, suspecting psoriatic erythroderma, cyclosporine 150 mg daily was administered with tapering of the prednisolone. Two weeks after a dose reduction of cyclosporine to 100 mg/day, erythroderma with widespread generalized pustules and fever developed. Histology of a biopsy revealed inflammatory infiltrates in the skin with a spongiform pustule of Kogoj, which was consistent with generalized pustular psoriasis (GPP). Her pustules improved with additional etretinate 20 mg/day, but the erythroderma persisted and she consulted us. Three sessions of granulocyte and monocyte apheresis once weekly were effective for her condition and decreased her serum levels of IL-6 and IL-8. She had homozygous mutations of c.[28C>T] in IL36RN which cause p.[Arg10Ter]. She is the oldest reported case of GPP with a deficiency of interleukin-36 receptor antagonist (DITRA), although GPP in DITRA has been suggested to usually occur in younger cases with no pre-existing psoriasis vulgaris.

There are several treatment methods for localized scleroderma, but treatment is difficult when the lesion is widely distributed. We encountered a case who was treated successfully with etretinate, a vitamin A derivative. The usefulness of this agent is discussed.

Lichen planus is an immune, infl ammatory reaction with characteristic clinical and histological lesions. It is a benign disorder, often chronic or recurrent, characterized by fl at-topped, pink to purple, shiny pruritic polygonal papules on the skin, or milky white reticular papules on the visible mucous membranes. Hypertrophic lichen planus is a chronic form of lichen planus with marked epidermal hyperplasia and intense pruritus. It is characterized by symmetrical hypertrophic plaques, usually located on the pretibial or perimalleolar regions. Lesions are often resistant to treatment. This paper presents a patient with a giant form of verrucous lichen planus on the lower extremities, with a chronic course and resistance to various forms of therapy (keratolytics, local and intralesional corticosteroids, radiotherapy, systemic antibiotics, cryotherapy). Significant improvement was seen after 8-month treatment with etretinate (initial dose of 75 mg per day, with progressive reduction to 10 mg per day). Etretinate therapy resulted in a significant regression of the disease.

Infantile generalized pustular psoriasis is a rare form of psoriasis and the best treatment is controversial. We experienced a 2-year-old female with erythema on her neck and axilla starting at 3 months of age. She presented with recurrent annular and geographic scaly erythema with a few pustules on the neck, precordium and axilla, but no fever. The histopathology revealed subcorneal neutrophilic infiltration and microabscesses without Kogoj's spongiform pustules. The initial diagnosis was subcorneal pustular dermatosis. However, she developed widespread geographic erythema and numerous pustules over her entire body with a fever when she got a cold. A second skin biopsy revealed monolocular pustules and Kogoj's spongiform pustules in the subcorneal layer. Etretinate was administrated after a diagnosis of pustular psoriasis was made and her condition improved gradually. The choice of treatment depends on patient age, general condition and the disease severity.

Background Generalized pustular psoriasis (GPP) is a chronic autoimmune disease characterized by fever, erythema, and neutrophilic pustules over large areas of the skin. GPP does not respond well to pharmacologic intervention. Objective We sought to assess efficacy of selectively depleting the myeloid lineage leukocytes in patients with GPP. Methods Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Eligible patients had more than 10% of their skin area covered by pustules. Treatment with oral etretinate, cyclosporine, methotrexate, prednisolone, and topical prednisolone/vitamin D3 was continued if had been initiated well in advance of study entry. Five sessions of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn (JIMRO Co Ltd, Takasaki, Japan) were administered (1 session/wk over 5 weeks) to selectively deplete Fcγ receptor and complement receptor bearing leukocytes. Efficacy was assessed by measuring the skin areas covered by pustules at baseline and 2 weeks after the last GMA session. Results One patient did not complete the first GMA session. Based on the GPP severity scores relative to entry, the overall scores improved (n = 14, P = .0027), and the area of erythroderma ( P = .0042), pustules ( P = .0031), and edema ( P = .0014) decreased. Likewise, Dermatology Life Quality Index improved ( P = .0016), reflecting better daily function and quality of life. Twelve patients were judged as responders (85.7%), and 10 patients maintained the clinical response for 10 weeks after the last GMA session without any change in medication. Limitations This study was unblinded and without a placebo arm. Conclusion GMA in this clinical setting was safe and effective, suggested a major role for granulocytes/monocytes in the immunopathogenesis of GPP.

UV-based therapies, which include narrow-band (NB) UVB, broad-band (BB) UVB, and psoralen and UVA (PUVA), are well known treatment options for moderate to severe plaque psoriasis. However, there are limited evidence-based reviews on their efficacy, short-term safety, and tolerability. The aim of the study was to evaluate the efficacy, short-term safety, and tolerability of UV-based therapy in the treatment of adults with moderate to severe plaque psoriasis. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating NB-UVB, BB-UVB, and PUVA in adults with moderate to severe plaque-type psoriasis. Our efficacy outcomes were ≥ Psoriasis Area and Severity Index (PASI)-75 and clearance. We evaluated the short-term safety and tolerability from the percentage of adverse effects and withdrawal due to adverse effects, respectively. Forty-one RCTs, with a total of 2,416 patients, met the eligibility criteria and were included in the analysis. In regard to PASI-75 in monotherapy trials, PUVA (mean: 73 %, 95 % CI 56–88) was the most effective modality. Trials with BB-UVB also showed a high PASI-75 (73 %) but with a wide CI (18–98) due to heterogeneity of the total available three studies. This was followed by NB-UVB (mean: 62 %, 95 % CI 45–79) then bath PUVA (mean: 47 %, 95 % CI 30–65). In regard to clearance in the monotherapy trials, PUVA (mean: 79 %, 95 % CI 69–88) was superior to NB-UVB (mean: 68 %, 95 % CI 57–78), BB-UVB (mean: 59 %, 95 % CI 44–72), and bath PUVA (mean: 58 %, 95 % CI 44–72). The percentages of asymptomatic erythema development in monotherapy trials were 64 % for BB-UVB, 57 % for NB-UVB, 45 % for PUVA, and 34 % for bath PUVA. Symptomatic erythema or blistering percentages for the monotherapy trials were as follows: 7.8 % for NB-UVB, 2 % for BB-UVB, 17 % for PUVA, and 21 % for bath PUVA. The percentages of withdrawal due to adverse effects were 2 % for NB-UVB, 4.6 % for BB-UVB, 5 % for PUVA, and 0.7 % for bath PUVA monotherapy trials. As a monotherapy, PUVA was more effective than NB-UVB, and NB-UVB was more effective than BB-UVB and bath PUVA in the treatment of adults with moderate to severe plaque-type psoriasis, based on clearance as an end point. Based on PASI-75, the results were similar except for BB-UVB, which showed a high mean PASI-75 (73 %) that was similar to PUVA, but with a wide CI (18–98). The short-term adverse effects were mild as shown by the low rate of withdrawal due to adverse effects.

Scleromyxedema is a rare progressive cutaneous mucinosis, usually associated with a systemic involvement and paraproteinemia. Its aetiology remains unknown. The therapeutic options include numerous treatment modalities, however, no standard treatment exists as the rarity of this disease prevents the execution of controlled therapeutic trials. This paper reports a case of a 38-year-old male with progressive scleromyxedema associated with gammopathy. Initially, the patient was treated with prednisolone and later etretinate was added to the therapeutic schedule with quite good clinical improvement. However, after 6 months of treatment, several adverse effects were observed: hypercholesterolemia, hypertriglyceridaemia and cataract of the right eye. The patient was consulted by dermatologists in Warsaw and Gdansk as well as by a haematologist. The patient was excluded from oncological treatment. Melphalan therapy was not recommended as it is associated with very toxic side effects. IVIG treatment (intravenous immunoglobulin) was not initiated because of financial issues. As the disease progressed, treatment with plasmapheresis was introduced. The patient received 4 cycles of the therapy. It was well-tolerated by the patient and gave satisfactory, but temporary results. In order to obtain long-lasting improvement the patient was treated with IVIG (21.0 g/dose for 5 consecutive days). This treatment modality seems to have resulted in a more stable improvement.

Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side-effects and cost. It is necessary to evaluate the effect of long-term psoriasis treatment, but there have been no reports evaluating long-term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long-term treatment with a combination of topical corticosteroid and topical vitamin D3 analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant.

The term retinoid includes both natural and synthetic derivatives of vitamin A. Retinoid-containing treatments have been used since ~1550BC by the early Egyptians. Treatment of ichthyosiform disorders with retinoids dates back at least to the 1930s. Early use of high-dose vitamin A demonstrated efficacy, but because vitamin A is stored in the liver, toxicity limited usefulness. Interest turned to synthetic retinoids in an effort to enhance efficacy and limit toxicity. Acetretin, isotretinoin and, in the past etretinate, have provided the most effective therapy for ichthyosiform conditions. They have been used for a variety of ages, including in newborns with severe ichthyosis and for decades in some patients. Careful surveillance and management of mucous membrane, laboratory, skeletal, and teratogenic side effects has made systemic retinoids the mainstay of therapy for ichthyosis and related skin types.

Acrokeratosis paraneoplastica Bazex (Bazex syndrome) is a rare paraneoplastic skin disease defined by erythematous, violaceous, scaly plaques on the hands and feet and on other acral locations such as nose and ears. Bazex syndrome is linked to a variety of underlying malignancies. Usually the skin lesions develop prior to the diagnosis of an internal malignant neoplasm with spontaneous remission after tumour removal. The objective of this study was to review the so far reported risk factors, diagnostic work-up, prognosis and treatment options for Bazex syndrome in a systematic manner. This systematic review is based on a search in MEDLINE, EMBASE and Cochrane Central Register for English and German articles from 1990 to 2015. Evidence on the diagnosis and treatment of Bazex syndrome is limited predominately to case reports or to small case series. There are no randomized controlled trials. A number of underlying tumour entities, predominately oropharyngeal neoplasms and tumours of the gastroenterological tract, but other malignancies were reported. Treatment modalities including topical and systemic corticosteroids, salicylic acid, topical vitamin D analogues, etretinate and PUVA therapy are often ineffective. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic review was to call attention to this rare condition and to help clinicians to diagnose and treat Bazex syndrome effectively. Because of the good prognosis of the skin lesions and the tendency to resolve spontaneously if the underlying tumour is treated early, the differential diagnosis of Bazex syndrome should be taken into consideration when dealing with atypical psoriasiform cutaneous lesions. An early diagnosis may improve the patient's prognosis substantially.

Milia en plaque (MP) is an uncommon skin condition, usually occurring in periauricular distribution, due to confluence of whitish smooth milia with formation of typical plaques. Lesions are usually asymptomatic, but in a minority of cases a slight sensation of burning or itching has been referred. Histologically MP is formed by laminated keratin-filled small cysts presenting at their periphery a few layer of flattened basaloid cells. Diagnosis is usually a clinical one; differential diagnosis can include milia secondary to a blistering disease, milia secondary to topically applied perfumes, or due to topical drugs, as corticosteroids or 5-fluorouracil, or oral drugs as benoxaprofen, milia after radiotherapy or mechanical traumas as well as other pathological skin conditions like familial or naevoid comedo sindrome, Favre-Racouchout disease, lichen planus tumidus folliculans. Oral minocycline or etretinate, topical tretinoin, electrodesiccation, CO2 laser, all have been proposed to treat MP, but oral therapy in some instances could be judged excessive, while topical retinoids can give rise to heavy inflammation and electrodesiccation and laser can lead to poor aesthetic results. A 32-year-old woman who presented with primary MP with bilateral retroauricolar localization was treated with cryosurgery, a single freeze-thaw cycle of 75 s. In about 8 weeks complete healing was observed in both areas. After 2 years of follow-up no recurrence was observed with no pigmentary side effects and a very good aesthetic results. Open spray cryosurgery can be suggested as first choice treatment for MP, this method appearing a safe, effective, well-tolerated, time-sparing and not expensive therapy.

Psoriasis, a common disease with variable clinical manifestation effect the quality of life. Prevalence of psoriasis varies from country to country, effect equally to male and female and all age groups. Pathogenesis of psoriasis seems to be genetically determined T-lymphocyte mediated disorder due to interaction between keratinocytes and lymphocytes. Various treatments used for treating psoriasis topical or systemic, clear the psoriasis lesions partially or completely, but are not able to produce prolong or permanent remission. Maximum remission period reported with all the known therapies are 1 year. Chief problem with all the therapies are relapses. Recently introduced azathioprine pulse therapy has been found to target specially to activated T-lymphocytes leading to long term remission and less organ toxicity. In this treatment azathioprine was used as intermittent high dose (IHD) i.e. 500 mg daily on 3 consecutive days repeated every month with continuous low dose azathioprine (CLD) 100 mg daily in between the IHD. It was divided into four phases. In phase I, treatment with IHD and CLD was continued till all the lesions of psoriasis clear. Methotrexate (MTX) 15-25 mg orally or subcutaneously weekly along with coal tar 6% was also given to clear the lesions fast. After all lesions clear patients enter into phase II where all the treatment is stopped except IHD and CLD which was given for 9 months to prevent any minor recurrence. At the end of 9 months if no recurrence occur IHD was stopped and patients take only CLD for another 9 months (Phase III). In phase IV CLD was also stopped and patients were followed up for any recurrence. With this therapy about 70 patients inter into phase IV i.e. remission for 1-10 years continuously after all treatment was stopped. Subsequently it was found clearing the psoriatic arthritis and nail changes in psoriasis also for prolonged period. Introduction Psoriasis a common dermatoses with extremely variable clinical manifestations is commonly present as well defined erythematous scaly plaques which become silvery on an attempt to scrap. Various types of psoriasis include plaque or vulgaris, guttate, pustular, erythrodermic, flexural, palmo-plantar, arthritis and nails psoriasis [1]. Prevalence of psoriasis varies from 0.12-8% all over world population [2]. It is more in cold climate. It affects equally to male and female. It is seen in all age group; however when it occurs in early age group its association with HLA B57 and B13 is more. Remission and relapses are very common in psoriasis. Various therapies used include topically coaltar [3], diathranol, corticosteroids with or without salicylic acid, calcipotriol [4], tazarotene and PUVA. Systemic therapies include [5] methotrexate [6,7], methotrexate +betamethasone [8], cyclosporine [9], PUVA, narrow band UVB, photo-therapy [10], hydroxyurea [11], azathioprine, retinoid like etretinate and acitretin [12-14] and biologics like etanercept and infliximabs [15]. All these treatment clear the psoriasis lesions partially or completely but are not able to prevent relapse or produce prolonged remission. Maximum remission period reported with these therapies is 1 year [16]. The chief problem in the management of psoriasis with various types of therapies is frequent relapses and subsequent need for repeated doses of systemic therapy leading to serious side effects. Repeated use of topical application usually leads to noncompliance by the patients. The goal of psoriasis treatment should be to control the disease process initially; to decrease percentage of involved body surface area, to achieve and maintain remission for prolonged period or permanently, to produce minimum adverse side effects and to improve patient’s quality of life. Thus the need for more specific systemic therapy which targets the T lymphocyte with the promise of long term remission and less organ toxicities is needed. Precipitating factor in psoriasis Trauma in the form of burn, cut and scratch may produce and localized the lesions (Koebner’s phenomenon). Usually winter aggravates and summer improves the disease. Infections: Bacterial infection especially streptococcal infection of upper respiratory tract, otitis media in children and infection in perianal area is associated with guttate psoriasis. Drugs: Like chloroquine, beta-blocker and lithium are presumed Correspondence to: Dr. Ramji Gupta, 47-C Pocket B Siddhartha Extension, New Delhi-110014, India, Tel: 91-11-26347405; E-mail: drramjigupta@yahoo.co.in

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory keratosis that is clinically characterized by gradually developing reddish or orange extending plaques and keratotic follicular papules. In pediatric patients, we frequently hesitate to administer certain medications for treatment of PRP, specifically etretinate, systemic corticosteroids, and biologics recommended by previous studies. Although administration of high-dose vitamin A was described in a previous textbook of dermatology, details about the lower limits and treatment periods were not provided. We presented a pediatric case of PRP that was successfully controlled with minimum dosage of systemic vitamin A in the literature. Before and 14 days after beginning the therapy, both vitamin A levels of peripheral blood were within the normal range. We considered that the clinical efficacy may not be due to a supplementary effect of vitamin A, but to a pharmacological action because serum vitamin A was within the normal limits during the therapy.

Alcohol has long been suspected to be a triggering and precipitating factor of psoriasis. Alcohol misuse is common in patients with moderate-to-severe psoriasis and appears to impair treatment outcome.In this article, the authors review the available data regarding the metabolic and toxicological interactions between anti-psoriasis systemic drugs and ethanol and/or alcoholic beverages. Special attention is given to the influence of alcohol consumption on the hepatotoxic risk of some anti-psoriasis drugs. The article was prepared using a MEDLINE literature search.The available knowledge highlights the existence of a few significant pharmacological interactions, such as the reduced exposure to cyclosporine by red wine, the possible increase of cyclosporine levels following a heavy acute alcohol intake, and, especially, the conversion of acitretin to etretinate, in the presence of ethanol, with important implications in females of child-bearing potential. There are limited data on the contributing role of alcohol in the hepatotoxicity induced by some anti-psoriasis drugs and the existing information on this topic is still controversial. However, further investigation is needed to assess the relevance of interactions between alcohol consumption and drug therapy for psoriasis, under both pharmacological and toxicological perspectives. Long-term prospective studies on large cohorts of patients are warranted to disclose the actual significance of such potential interactions in clinical practice.

A survey of psoriasis patients from 1982-2001 has been reported by the Japanese Society for Psoriasis Research. The aim of this study is to analyze psoriasis patients in Japan registered from 2002-2008. A total of 11 631 cases were registered from 152 dermatological institutions in Japan. Males (7738 cases, 66.5%) were predominant over females (3893 cases, 33.5%). The clinical types of psoriasis were psoriasis vulgaris (88.5%), guttate psoriasis (3.9%), psoriasis arthropathica (3.3%), generalized pustular psoriasis (1.3%), psoriatic erythroderma (1.2%), localized pustular psoriasis (0.9%) and infantile psoriasis (0.1%). Topical corticosteroids (85.4%) and vitamin D(3) (59.7%) products were the main previous topical agents. Previous systemic treatments included etretinate (8.8%), cyclosporin (8.3%) and methotrexate (2.0%). Use of topical vitamin D(3) and systemic cyclosporin therapies has been increasing during the past 7 years. Topical psoralen and ultraviolet A therapy (PUVA) (7.6%) was the predominant phototherapy followed by UV-B (7.3%) and systemic PUVA (4.7%). Use of UV-B phototherapy has been increasing during the past 5 years. The survey of Japanese psoriasis patients during 2002-2008 disclosed that psoriasis arthropathica is more prevalent (1%) than that of the previous survey during 1982-2001. Use of topical vitamin D(3) and systemic cyclosporin has been increasing during the past 7 years.

A hiperceratose epidermolítica é uma forma de ictiose geralmente resistente a tratamentos tópicos. Relata-se um caso de paciente feminina , em acompanhamento na dermatologia desde 1978, com diagnóstico de hiperceratose epidermolítica. Foi tratada inicialmente com queratolíticos, vitamina A oral, ácido tartárico e emolientes tópicos, porém sem melhora no quadro clínico, já que não haviam disponíveis outros tratamentos na época. Em 1986, com o advento dos retinóides orais, foi introduzido o etretinato, e em 1998, foi substituído pelo acitretin, apresentando excelente resposta terapêutica. No momento a paciente está em uso de acitretin 25 mg/dia, completando 23 anos de uso de retinóides orais, com mínimos efeitos adversos e melhora significativa na qualidade de vida Epidermolytic hyperkeratosis is a form of ichthyosis normally resistant to topical treatments. Female patient monitored since 1978 diagnosed with epidermolytic hyperkeratosis. Clinical examination showed generalized hyperkeratosis and scaling. Given that no other treatments were available at the time, the patient was initially treated with keratolytic, systemic vitamin A and moisturizers, with no improvement. In 1986, with the development of oral retinoids, etretinate was introduced. In 1998 this was replaced by acitretin. The patient is receiving 25 mg/day after 23 years of using oral retinoids. Significant improvement of the condition and patient's quality of life has been noted

Background: Acute generalized pustular psoriasis (AGPP) is a rare variant of psoriasis that can be lethal without proper treatment. It can be caused by the withdrawal of corticosteroids and, among its extracutaneous manifestations, liver abnormalities are frequently under-reported or attributed to drugs. Objective: The aim of this study was to assess the clinical and laboratory data, treatment options, and disease outcome in patients with AGPP and to search for significant differences between subgroups of these patients. Study Design: This was a retrospective analysis of the clinical files from inpatients with AGPP observed in our department between 1973 and 2008. Statistical tests were performed at a significance level of 5%. Setting: This was an inpatient, single-center study. Main Outcome Measures: Outcome measures were a previous history of psoriasis, corticosteroid use before admittance, mortality rate, white blood cell count, absolute neutrophil count, and abnormalities in liver enzymes. Results: Atotal of 34 patients fulfilled the inclusion criteria, of whom 61%were men and 65%had a previous history of psoriasis vulgaris. Topical corticosteroids were applied by 50%of patients before admittance. Skin lesions remitted with methotrexate, etretinate, or acitretin treatment in all but two patients who died of sepsis. Abnormalities in liver enzymes were present in 47%of patients. Patients without a previous history of psoriasis had a significantly younger age at the first episode of AGPP. In the comparison between the groups of patients with and without liver abnormalities, a male preponderance and higher leukocyte counts were found in the former, with a positive correlation between the absolute neutrophil count and total bilirubin also being observed. Previous use of retinoids or methotrexate was not associated with these hepatic alterations. Limitations: Limitations of the data were that this was a single-center, retrospective study with a small sample size. Conclusions: Withdrawal of systemic or topical corticosteroids can precipitate or worsen AGPP and these agents should not be used in these patients. Liver abnormalities can be considered an extra-cutaneous manifestation of AGPP. As in other series, no association between the use of drugs and changes in liver tests was found and therefore the deleterious withdrawal of efficient drugs, namely acitretin and methotrexate, should be avoided.

Background Although cyclosporin (CyA) has been in use in psoriasis for more than 20 years, there is still controversy regarding treatment strategy, monitoring of kidney function and utility in non-plaque psoriasis. Objectives To prepare for evidence-based recommendations concerning the practical use of CyA in psoriasis, we performed a systematic review to better define treatment strategy, risk of kidney toxicity and evidence for use in non-plaque psoriasis. Methods A systematic search was performed on PubMed, Cochrane and Embase databases, using the key-words ‘psoriasis’, ‘CyA’, ‘nephrotoxicity’ during the period from 1980 to June 2010. Results The initial literature search identified 428 articles. The final selection included 16 randomized controlled trials (RCT) for treatment strategy, 25 articles (histological studies and RCT) for risk of kidney toxicity and 10 articles (RCT, prospective studies and case series) for use in non-plaque psoriasis. Higher doses of CyA of 5 mg/kg produced Psoriasis Area Severity Index (PASI) 75 response in between 50 and 97% of patients, whereas lower doses of 2.5 mg/kg yielded PASI 75 in between 28 and 85%. CyA could maintain remission at doses of at least 3 mg/kg/day. Low calory diet in obese patients was shown to improve CyA efficacy. More than 50% of the patients treated with CyA may have an increase in serum creatinin value over 30% of baseline if treatment is prolonged for 2 years. CyA at a dose of 2.5 mg/kg/day was effective for 89% of patients with palmoplantar pustulosis. More than 50% of the patients with erythrodermic psoriasis obtained a significant improvement at doses between 3 and 5 mg/kg/day at 2–4 months. CyA was more effective than etretinate on nail psoriasis. Conclusion Oral CyA is indicated for patients with plaque psoriasis, pustular psoriasis or erythrodermic psoriasis. The starting dose of 5 mg/kg is associated with a higher degree of clearance. The benefit-risk appears to be better for patients without risk factors for nephrotoxicity: non-obese patients without hypertension and aged below 60. Although CyA is ideally suited for crisis intervention, continuous maintenance treatment with CyA may be envisaged in some patients provided serum creatinin is regularly monitored and the cumulative treatment duration is preferably limited to 2 years or less.