Efficacy of Omalizumab for the treatment of Bullous Pemphigoid. Spanish multicenter real-world experience.

BACKGROUND: Bullous Pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are elderly and associate multiple comorbidities. Topical and systemic corticosteroids are considered as the first-line treatment for BP and immunosuppressors are used as steroid-sparing treatments but both have side effects and contraindications which are even more common in this elderly population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease this side effects while achieving equal or better effectiveness response rates.Omalizumab is a monoclonal antibody that targets IgE that has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES AND METHODOLOGY: To assess the efficacy and security of Omalizumab for the treatment of BP, we carried out a multicenter, retrospective, observational study including patients diagnosed of BP who received omalizumab for at least 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment was measured and we evaluate the possible correlation with clinical response. We excluded patients treated with Omalizumab for less than 3 months as we consider this duration is insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment we used the percentage of BSA improvement. RESULTS: We included 36 patients. The vast majority associate multiple comorbidities and all patients had used other systemic therapies apart from corticoids before Omalizumab.83% experienced some kind of treatment response and 42% of all patient treated achieved complete response.We did not find any correlation between higher levels and a better response (p=0,1791).All patients tolerated Omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it obtained clinical response in most patients and nearly half of the cases achieving complete response. It showed no side effects which is crucial in elderly patients suffering from BP.

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Tildrakizumab is a humanized, IgG1/κ antibody that interacts with the p19 subunit of interleukin 23. It is approved for the treatment of moderate-to-severe plaque psoriasis. Real-world evidence on the effectiveness and safety of tildrakizumab is limited. OBJECTIVES: To assess the effectiveness and safety of tildrakizumab at 24 weeks in patients with moderate-to-severe plaque psoriasis in routine clinical practice. METHODS: Retrospective, observational, multicentre study including adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab under real-life conditions. Patient data were extracted from anonymized electronic medical records. Statistical analysis was performed using SPSS22. RESULTS: A total of 190 patients were included. About 53.9% were men with a mean age of 51.45 (SD 3.9) and a mean BMI of 29.13 (SD 6.21). About 79.8% (132 out of 190) of patients had previously received biological therapy (BT) and 17.3% (33 out of 191) had psoriatic arthritis. Baseline PASI was 10.7 (SD 6.53). Up to 109 patients reached Week 24 and at this point mean baseline PASI decreased to 1.7 (SD 4.8), representing an 88.79% mean PASI reduction. At 6 months, 87.1% and 40.3% of the treated patients achieved PASI ≤3 and ≤1, respectively. At Week 24 mean BSA decreased from 13.2 (SD 10.07) to 1.6 (SD 4.40) and mean DLQI went from 12.5 (SD 7.12) to 1.2 (SD 3.27). Multivariate analysis showed no differences when effectiveness was correlated with gender, obesity, psoriatic arthritis or prior exposure to BT. The rate of adverse events (AE) was 5.9% (11 out of 190), where infections were the most frequent AE (4 out of 11). One patient suffered a haemorrhagic ictus and one patient died due to causes unrelated to the study. CONCLUSION: Tildrakizumab was effective and safe in a large cohort of patients with moderate-to-severe plaque psoriasis treated in a routine clinical setting.

Upadacitinib effectiveness in moderate-to-severe atopic dermatitis: A real-life multicentre and retrospective study.

This was an observational and retrospective multicentre study conducted on adolescents and adults diagnosed with moderate-to-severe atopic dermatitis (AD) and treated with upadacitinib. Disease severity was measured by Eczema Area and Severity Index (EASI), validated investigator global assessment for AD and pruritus Numerical Rating Scale (NRS) at baseline and Weeks 4, 16, 24 and 52 (when available). Twenty-one patients were included. All patients had previously received topical and systemic corticosteroids. Rapid response to upadacitinib was observed: Mean (SD) EASI score was 19.8 (6.5) at baseline, and 3.1 (4.2), 0.9 (1.4), 0.6 (0.6) and 0.6 (0.6) at the Weeks 4, 16, 24 and 52, respectively. Itch was controlled at Week 4 in all patients (mean [SD] NRS score 7.6 [1.9] baseline, 1.5 [1.3] W4). Severe infections or major adverse cardiovascular events were not reported. We highlight effectiveness and rapid response of upadacitinib in achieving itch control even in long-standing recalcitrant cases.

Clinicopathological characteristics of cutaneous and mucocutaneous leishmaniasis in patients treated with TNF-α inhibitors.

BACKGROUND AND OBJECTIVES: The increasing use of biologics in the treatment of inflammatory diseases has led to more cases of leishmaniasis in patients subjected to iatrogenic immunosuppression. The main objective was to describe the characteristics of the patients with cutaneous (CL) or mucocutaneous (MCL) leishmaniasis who were receiving a biological therapy at the time of diagnosis. PATIENTS AND METHODS: A multicenter retrospective study was design based on a cohort of patients diagnosed with CL or MCL. All patients who were being treated with biologicals were included. For each case, two matched non-exposed patients were included for comparison. RESULTS: 38 patients were diagnosed with CL or MCL while being treated with tumor necrosis factor alpha (TNF-α) inhibitors. Leishmaniasis presented more frequently as a plaque (58.3%) with a larger median lesion size (2.5 cm), ulceration (92.1%), and required a greater median number of intralesional meglumine antimoniate infiltrations (3 doses) (P < 0.05) than in non-exposed patients. We found no systemic involvement in patients being treated with anti-TNF-α. We did not find differences regarding the treatment characteristics whether biologic therapy was modified or not. CONCLUSIONS: Although management should be individualized, maintenance of biologic therapy does not seem to interfere with treatment of CL or MCL.

Guselkumab effectiveness, and posology in patients with moderate to severe hidradenitis suppurativa: A retrospective bicentric experience.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recalcitrant skin disease of the terminal hair follicle. Therapeutic alternatives in HS are limited nowadays. Adalimumab, is the only approved biological treatment for patients with moderate to severe HS, and some patients do not reach an optimal response, or experience a progressive response loss, needing therapeutic alternatives. IL-23 pathway is also involved in HS pathogenesis, so its blockade could contribute to reach disease control. Guselkumab is a monoclonal antibody targeting the p19 subunit of extracellular IL-23, currently approved for psoriasis in adults, and recently some authors have reported its effectiveness in patients with moderate to severe HS refractory to other systemic treatments, becoming a hope for some patients. However adequate dosing and intervals have not been determined yet, so in most published series, doses approved for psoriasis are commonly used. On this topic a retrospective bicentric study including HS patients treated with guselkumab in the dermatologic departments of university hospitals Puerta de Hierro of Majadahonda (Madrid, Spain) and Doctor Peset of Valencia (Valencia, Spain) was conducted. We reported effectiveness, dosage and frequency of administration in the cohort, in order to establish the most effective dosage regimen and to clarify the potential role of guselkumab for this disease.

A prospective multicenter study assessing effectiveness and safety of secukinumab in a real-life setting in 158 patients.

BACKGROUND: Secukinumab is a first-in-class interleukin 17A monoclonal antibody that has demonstrated an excellent safety and efficacy profile in phase 3 studies. OBJECTIVE: To evaluate the effectiveness of secukinumab in daily clinical practice and to understand the clinical and epidemiologic characteristics of patients treated with secukinumab in clinical settings. METHODS: In this multicenter prospective observational study, we recruited adult patients with moderate-to-severe plaque psoriasis from 12 hospitals in Spain during January-December 2016. These patients were treated with secukinumab and prospectively followed at 12-week intervals for 52 weeks. RESULTS: In total, 158 patients were recruited to the study. A Psoriasis Area and Severity Index (PASI) score improvement ≥75% over baseline (PASI-75) was achieved by 57%, 83.5%, 89%, and 78.5% of patients at weeks 4, 12, 24, and 52, respectively. PASI-90 was achieved in 27.8%, 62%, 64.6%, and 63.2% of patients at weeks 4, 12, 24, and 52, respectively; PASI-75 and PASI-90 responders were significantly more common among patients with a body mass index <30 kg/cm2 and patients without previous biologic therapy failures. LIMITATIONS: Observational study. Time from onset of psoriasis was not evaluated. CONCLUSION: Secukinumab is a safe treatment with effectiveness rates similar to those found in its phase 3 studies. These rates endure up to a year from start of treatment.

Endogenous ochronosis: when clinical suspicion prevails over histopathology.

Endogenous ochronosis (EO) or alkaptonuria is an inherited autosomal recessive disease caused by the insufficiency of the enzyme homogentisic acid dioxygenase. This disturbance causes an accumulation and increased renal excretion of homogentisic acid (AHG), which manifests as dark urine when it oxidizes on contact with air. Other clinical manifestations of OE are the result of the deposit of AHG in the form of ochronotic pigment at the level of collagen in the skin and cartilage, where it causes blue-gray cutaneous hyperpigmentation, degenerative arthropathy, valvular disease, and other multisystem effects. Despite the progressive and irreversible nature of OE and the lack of a curative treatment, the life expectancy is preserved. We report a new case of EO with cutaneous and joint involvement, in which a high clinical suspicion, confirmed by elevated AHG in urine was the key in the diagnosis.

Exogenous ochronosis: the failure of depigmenting creams.

Exogenous ochronosis (EO) is an entity that manifests as black-bluish or grayish-brown cutaneous hyperpigmentation, which is a consequence of the deposition of ochronotic pigment with characteristic banana-like morphology between the collagen fibers of the dermis. Both the clinical presentation and histopathology appearance are superimposable with endogenous ochronosis or alcaptonuria, a hereditary disease in which ochronotic pigment deposition occurs at a multisystemic level. The most frequent cause of EO is the use of facial depigmenting creams containing hydroquinone, a common practice among women with high phototypes. We present a woman who developed EO on the face, upper chest, and back after prolonged use of a depigmenting cream containing hydroquinone.

[Actinic keratosis: New concept and therapeutic update]. / Queratosis actínica: nuevo concepto y actualización terapéutica.

Actinic keratosis (AK) is a common reason for consultation in both Primary Care and Specialised Care. It is the third or fourth most common reason for consultation in dermatology, accounting for up to 5-6% of patients attended. It has also been observed that its prevalence has been increasing in the last 10years, compared to other dermatoses. This is also expected to continue to increase due to longer life expectancy, and by the changes in sun exposure habits since the middle of the last century. The aim of this article is to update the concepts of AK, cancerisation field and to present the currently available therapeutic tools.

Diclofenac sodium 3% gel for darier's disease treatment.

BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder which causative gene, ATP2A2, is located atchromosome 12q23-24. The lesions of DD are skin-coloured to brown, hyperkeratotic, greasy papules that coalesce into warty plaques commonly involving the seborrhoeic areas of the trunk and face, especially the scalp margins, temples, ears, and scalp. The most common complaint associated with the disease is itching, with exacerbations attributed to heat, sweating, sunlight, lithium, steroid therapy, stress, and menstruation OBJECTIVES: We report a patient with DD treated with topical diclofenac sodium 3%. METHODS: We report a 33-year-old patient with Darier's Disease. He was followed in our department since 2009, and we had tried to control several flares of lesions during follow-up, but oral isotretinoin was not tolerated because of adverse effects; and oral doxycycline showed lack of efficacy.At April 2014, patient presented with new lesions, involving anterior chest wall, abdomen, back and shoulders areas. We started with diclofenac sodium 3% in hyaluronic acid 2.5% once daily, only applied at abdomen and anterior chest wall. RESULTS: After six-month therapy, hyperkeratotic papules were flattened and less harshness of them was noticed, even some of them disappeared. CONCLUSIONS: We consider topical diclofenac therapy as a useful alternative treatment for DD patients, in which previous therapies have not shown efficacy. We did not observed topical adverse effects, neither systemic absorption symptoms, but werecognized further and larger studies are needed to asses the efficacy and safety of this treatment in DD.

Granuloma faciale treatment with tacrolimus.

We present a 40-year-old woman with a one-year history of a solitary and asymptomatic facial lesion. On physical examination a slightly infiltrated, smooth red to brown nodule was seen at the left malar region. A biopsy established the diagnosis of granuloma faciale. After two-months therapy with topical tacrolimus 0,1%, nodule was resolved.