A new phototherapy regimen during winter as an add-on therapy, coupled with oral vitamin D supplementation, for the long-term control of atopic dermatitis: study protocol for a multicentre, randomized, crossover, pragmatic trial - the PRADA trial.

BACKGROUND: Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates. METHODS: This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter. DISCUSSION: This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02537509 , first received: 1 September 2015.

Idiopathic Facial Aseptic Granuloma in a 13-Year-Old Boy Dramatically Improved with Oral Doxycycline and Topical Metronidazole: Evidence for a Link with Childhood Rosacea.

Idiopathic facial aseptic granuloma (IFAG) is a rare, benign pediatric dermatological lesion that occurs in children between 8 months and 13 years of age. The pathogenesis of IFAG is still unclear but it is likely to be associated with granulomatous rosacea in childhood. Here we describe a case of IFAG in a 13-year-old boy who showed a dramatic response to oral doxycycline and topical metronidazole, which supports the hypothesis that IFAG may belong to the spectrum of rosacea.

Psoriasiform Diaper Rash Possibly Induced by Oral Propranolol in an 18-Month-Old Girl with Infantile Hemangioma.

Propranolol, a nonselective blocker of ß-adrenergic receptors, has become the first-line treatment for complicated infantile hemangiomas. Therefore, its use in the pediatric population has expanded in recent years. In adults, ß-blockers have been reported to be the most common causative agents for drug-induced psoriasis. In infants treated with propranolol for infantile hemangioma, the onset of psoriasiform diaper rash has not yet been reported. Here, to the best of our knowledge, we report the first case of psoriasiform diaper rash possibly induced by oral propranolol in an 18-month-old girl with no family history of psoriasis.

Extensive Darier Disease Successfully Treated with Doxycycline Monotherapy.

Darier disease (DD) is a rare dominantly inherited genodermatosis characterized by loss of intercellular adhesion (acantholysis) and abnormal keratinization. DD is often difficult to manage. Numerous treatments have reportedly been used for the treatment of DD, with limited success. Systemic retinoids are considered the drug of choice for treating DD. However, their use is limited by potential deleterious side effects. Considering the recently reported efficacy of doxycycline for Hailey-Hailey disease, an inherited acantholytic skin disorder pathogenetically similar to DD, we report the case of a patient with extensive DD who showed a dramatic response to oral doxycycline monotherapy.

Wells' Syndrome Mimicking Facial Cellulitis: A Report of Two Cases.

Wells' syndrome (WS), or eosinophilic cellulitis, is an uncommon inflammatory dermatosis of unknown etiology that typically presents with pruritic cellulitis-like plaques on the extremities. Therefore, WS is often misdiagnosed as bacterial cellulitis due to its similarity in presentation. Here, we report two cases of WS that masqueraded as bacterial facial cellulitis. Under treatment with oral prednisone and/or a combination therapy with levocetirizine and hydroxyzine, both patients showed a dramatic improvement of the skin lesions. These cases highlight the need for clinicians to consider WS in the differential diagnosis when evaluating a patient with facial cellulitis that does not respond to an initial antimicrobial regimen. In addition, our cases suggest that combination therapy with levocetirizine and hydroxyzine may be successfully used as corticosteroid-sparing treatment or to prevent relapse after the discontinuation of corticosteroid treatment.

Incomplete kawasaki disease in an elderly man.

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology, affecting predominantly young children. Here, we describe an unusual case of a 75-year-old man with several unique features of incomplete KD. Healthcare professionals should therefore be aware of the importance of considering KD at any age, even among elderly individuals. This case also highlights the usefulness of the algorithm proposed for children to diagnose incomplete KD in adults.

Nodal Melanoma Metastasis under Infliximab Therapy in a Patient with Nevoid Melanoma First Misdiagnosed as Benign Nevus: A Potentially Dangerous Diagnostic Pitfall in the Era of Biologic Therapies.

We report the case of a 53-year-old Caucasian woman who developed nodal melanoma metastasis under infliximab therapy 2 years after the removal of a nevoid melanoma, which was initially misdiagnosed as a benign compound nevus. This case illustrates the potential link between tumor necrosis factor (TNF)-α inhibition and the reactivation of latent melanoma. Furthermore, this case highlights the need for a complete skin examination before using anti-TNF-α therapy to rule out atypical malignant lesions or melanomas that can easily be missed because of presentations such as nevoid melanoma.

Dramatic response of nail psoriasis to infliximab.

Nail psoriasis, affecting up to 50% of psoriatic patients, is an important cause of serious psychological and physical distress. Traditional treatments for nail psoriasis, which include topical or intralesional corticosteroids, topical vitamin D analogues, photochemotherapy, oral retinoids, methotrexate, and cyclosporin, can be time-consuming, painful, or limited by significant toxicities. Biological agents may have the potential to revolutionize the management of patients with disabling nail psoriasis. We present another case of disabling nail psoriasis that responded dramatically to infliximab.

Leser-Trélat Sign without Internal Malignancy.

Leser-Trélat sign is characterized by the abrupt appearance of multiple seborrheic keratoses in association with underlying malignant disease. A case of Leser-Trélat sign in a 66-year-old healthy woman is presented. Evaluation and follow-up for the development of malignancy over a 2-year period failed to reveal any evidence of malignancy. To date, almost all cases of Leser-Trélat sign have been reported in association with an underlying malignancy. It is less known that Leser-Trélat sign can also occur in healthy individuals in the absence of internal malignancy.