Topical Tacrolimus 0.1% for treatment of cutaneous microcystic lymphatic malformations.

Microcystic lymphatic malformations as described in the international literature form a subgroup of low-flow congenital vascular malformations (VM) resulting from irregular embryological development. Microcystic lesions normally manifest as an accumulation of lymph- and blood-filled vesicles that, when externalized, cause skin maceration with consequent pain and potential infection resulting in the impairment of the patient's quality of life. There is no consensus on a standardized algorithm nor clear guidelines for successful treatment of this type of lymphatic malformation, and treatment options employed often result in ambivalent and transient outcomes with a high rate of recurrence. The topical formulation of tacrolimus is a well-known FDAapproved anti-T cell agent that was recently identified as a potent activator of ALK1, which is involved in several processes and functions including angiogenesis. We investigated if topical administration of tacrolimus may be an effective therapy for directly targeting cutaneous microcystic lymphatic malformations as a complement to systemic treatment. The study enrolled four patients with cutaneous microcystic lymphatic malformations: three male (ages: 13,15,18) and one female (age: 30). Two of the patients presented lesions on their backs, one patient on the left hand and one on the left lower limb. All four patients received treatment with topical tacrolimus 0.1% twice a day for 10 weeks on a previously selected area for application. Weekly clinical follow-ups were conducted along with close physician-patient contact. All patients displayed a satisfactory response after treatment. Lymphorrhea and bleeding were stopped in all cases and the esthetic aspect of lesions improved in two patients. To date, all patients presented no clinically significant changes to the size or extension of the lesion. Topical tacrolimus treatment is a promising and reasonable option for microcystic lymphatic malformations. Our results encourage further exploration in larger populations with the consideration that it is a safe and effective alternative or complementary therapy to systemic treatment.

Occlusive treatment enhances efficacy of tacrolimus 0.1% in a pediatric patient with severe alopecia areata: Case report and literature review.

Tacrolimus is an immunomodulatory drug, available for topical and systemic treatment of several dermopathies that are characterized by immune dysregulation. In the case of alopecia areata, standard application has proven insufficient to yield satisfactory results. Herein, we present a 6-year-old patient with Down syndrome who was treated with topical tacrolimus 0.1% ointment under occlusion overnight with remarkable clinical improvement within 4 months.

Tacrolimus tópico nas lesões cutâneas refratárias da dermatomiosite juvenil / Topical tacrolimus in refractory skin lesions of juvenile dermatomiosytis

A dermatomiosite juvenil (DMJ) é uma doença inflamatória crônica idiopática que afeta principalmente músculos e pele. As lesões cutâneas podem persistir apesar do controle bem-sucedido da miosite. O tacrolimus tópico é um novo agente imunossupressor que tem sido usado no tratamento da dermatite atópica, com poucos relatos de seu uso em miopatias inflamatórias na faixa etária pediátrica. Foram descritos três pacientes com DMJ (dois meninos) com idade atual de 5,7 a 10,6 anos. A terapia inicial administrada para esses pacientes foi: corticosteróide (sistêmico em três e tópico em um), antimalárico em três e metotrexato em dois. Todos apresentavam lesões cutâneas refratárias (eritema malar, eritema difuso e/ou vasculite cutânea) após melhora significativa da fraqueza muscular. Tacrolimus tópico 0,03 por cento foi usado duas vezes ao dia após falha do tratamento prévio. As características das lesões foram avaliadas de acordo com a extensão e a gravidade no início do uso do fármaco e após oito e 16 semanas. Na segunda avaliação (oito semanas), notavelmente um paciente apresentou melhora completa do eritema malar e do eritema difuso em membros e tronco, e dois tiveram melhora parcial do eritema malar e da vasculite cutânea. Na terceira avaliação (16 semanas), dois pacientes tiveram resolução completa das lesões e um apresentava eritema malar persistente e eritema moderado em glúteos e região lombar. No último paciente, a melhora das lesões cutâneas foi alcan-çada apenas após o uso de ciclosporina por 16 semanas. Nenhum deles teve efeitos adversos. Tacrolimus tópico pode ser considerado em pacientes com DMJ e manifestações cutâneas refratárias. Estudos posteriores controlados e randomizados com esse fármaco devem ser realizados nessa doença inflamatória.

Juvenile dermatomyositis (JDM) is a rare idiopathic chronic inflammatory disease that affects mainly muscle and skin. Cutaneous lesions may persist despite successful treatment of myositis. Of note, topical tacrolimus is a new immunosuppressive agent that has been used to treat atopic dermatitis with few reports in pediatric inflammatory myopathies. Three JDM patients (two males) were described, current age from 5.7 to 10.6 years. The initial therapy administered for these patients were: corticosteroid (oral in three and topical in one), antimalarial in three and methotrexate in two. All of them had refractory skin lesions (malar rash, extensive rash and/or cutaneous vasculitis) after significant improvement of muscle weakness. Topical tacrolimus 0.03 percent was used twice daily after failure of previous treatment. The features of lesions were evaluated according to extension and severity at start of drug and after 8 and 16 weeks. At the second evaluation (8 weeks), remarkably one patient had complete improvement of malar rash and extensive rash in limbs and trunk, and two had partial improvement of malar rash and cutaneous vasculitis. At the third evaluation (16 weeks), two patients had complete resolution of lesions and one had persistent malar rash and moderate lumbar and gluteus rash. In the last patient, the improvement of skin lesions was reached only after 16 weeks of cyclosporine use. None of them had adverse effects. Topical tacrolimus could be considered in JDM patients with refractory cutaneous manifestations. Further randomized controlled trials with this agent should be performed in this inflammatory disease.