Fibroadipose vascular anomaly treated with sirolimus: Successful outcome in two patients

Fibroadipose vascular anomaly (FAVA) is a rare, complex mesenchymal malformation combining fibrofatty replacement of the affected muscles and slow‐flow vascular malformation. The condition is characterized by localized swelling, severe pain, phlebectasia, and contracture of the affected limb. Treatment paradigms are not well established for this rare, recently recognized condition. We report two cases of FAVA in which treatment with sirolimus produced rapid, dramatic improvement in pain and quality of life.     

Delayed ulceration following combination pulse dye laser and topical sirolimus treatment for port wine birthmarks: A case series

Port wine birthmarks (PWB) are capillary vascular malformations within the papillary and reticular dermis, most commonly occurring on the head and neck and may darken and thicken with age. Pulsed dye laser (PDL) is the gold standard of treatment for PWB as it selectively targets involved vessels. Sirolimus is a macrolide antibiotic that selectively inhibits mammalian target of rapamycin, thereby suppressing the angiogenesis pathways that can be activated by PDL. Sirolimus and PDL may be used together to treat PWB. We present a case series describing three cases of delayed ulceration and systemic sirolimus absorption following combination therapy, highlighting a potential complication and patient safety concern.     

Generalized lymphatic anomaly successfully treated with long‐term,low‐dose sirolimus

Generalized lymphatic anomaly is a rare, complex, lymphatic anomaly generally involving soft tissues, spleen, and bones. It can lead to focal skeletal fragility and pathologic effusions. A recent prospective trial of sirolimus for complicated vascular anomalies showed partial response in seven patients with generalized lymphatic anomaly treated with sirolimus with a target trough level of 10‐15 ng/mL for 1 year (Adams et al). We describe successful treatment of generalized lymphatic anomaly with a lower‐dose, long‐term course of sirolimus.     

Successful combination therapy of propranolol and prednisolone for a case with congenital Kasabach–Merritt syndrome

A male fetus was delivered by cesarean section with a large hemangioma on his right chest and thrombocytopenia. Clinically, Kasabach–Merritt syndrome (KMS) was suspected, and immediately he was treated with daily prednisolone (PSL) 1 mg/kg and recombinant thrombomodulin without response. Additional propranolol (1–3 mg/kg per day) and increased PSL 2 mg/kg per day therapy successfully controlled his disseminated intravascular coagulation and decreased the tumor size without serious side‐effects. No relapse of KMS was observed after cease of PSL and propranolol. Combined use of propranolol and corticosteroid is expected as a candidate therapeutic tool for KMS.     

Preventive treatment with oral sirolimus and aspirin in a newborn with severe Sturge‐Weber syndrome

Sturge‐Weber syndrome (SWS) is characterized by facial capillary malformation, leptomeningeal capillary malformations, and choroidal and episcleral vascular malformations. These malformations produce neurologic and ophthalmological symptoms including seizures and glaucoma. A premature male newborn without prenatal diagnosis presented with severe bilateral SWS and was started on systemic sirolimus and aspirin. The patient has remained seizure‐free for 23 months and demonstrated an excellent response to pulsed dye laser treatment.     

Pyogenic granuloma over the venous component of a mixed vascular malformation

A 52‐year‐old man presented with a rapidly growing red tumor on the central neckline. It had appeared over a congenital flat and pinkish vascular lesion that involved the shoulder and the upper anterior area of his chest. Intermingled with the pinkish stain, there were also some blue nodules several millimeters in diameter. Histopathologic examination revealed that the full lesion was a mixed venous‐capillary malformation. The red tumor was excised and diagnosed as a pyogenic granuloma developing over the venous component of the vascular malformation. To our knowledge, a pyogenic granuloma growing over a venous malformation has not been previously described.     

Propranolol-resistant infantile hemangioma successfully treated with sirolimus

Infantile hemangiomas are the most common benign vascular tumors in childhood. Propranolol is the first-line treatment for infantile hemangiomas, but failures may occur. Sirolimus, an mTOR inhibitor, is a promising drug for the treatment of vascular malformations and vascular tumors. We present the case of a child with multiple infantile hemangiomasthat was successfully treated with sirolimus and propranolol after failure of combined propranolol and prednisolone treatment.     

Lower lip capillary malformation associated with lymphatic malformation without overgrowth: Part of the spectrum of CLAPO syndrome

Characteristic lower lip capillary malformation of CLAPO syndrome (Capillary malformation of the lower lip, Lymphatic malformations of the face and neck, Asymmetry, and Partial or generalized Overgrowth) may also occur as an isolated lesion or with only minor anomalies, supporting the concept that there is a spectrum of abnormalities in CLAPO syndrome. Preliminary studies have demonstrated mosaic activating mutations in PIK3CA.     

Topical sirolimus therapy for epidermal nevus with features of acanthosis nigricans

We present a 4‐year‐old developmentally appropriate boy with short stature and widespread expanding epidermal nevus with features of acanthosis nigricans. He was found to have a mosaic mutation in FGFR3, the R248C variant. Despite several therapies, he continued to have growth, fissuring, and bleeding of the affected skin. Ultimately, topical sirolimus was attempted and found to improve thickness and overall symptoms.     

Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial

BACKGROUND: Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. OBJECTIVES: To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. METHODS: In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. RESULTS: A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control. CONCLUSIONS: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.     

Atypical capillary malformations with subsequent diplegia: A difficult case of capillary malformation-arteriovenous malformation syndrome

Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a rare condition associated with mutations in the genes RASA1 and EPHB4. We present a challenging case of CM-AVM in a 17-month-old boy with permanent diplegia from an undiagnosed arteriovenous malformation underlying a large atypical capillary malformation over the lower thoracic spine. This case demonstrates that clinicians should have a low threshold for neuroimaging in the context of new neurologic symptoms in patients with atypical capillary malformations.     

Topical sirolimus as an effective treatment for a deep neurofibroma in a patient with neurofibromatosis type I

A 14‐year‐old boy with neurofibromatosis type I (NF1) presented with a painful neurofibroma on his right palm. The lesion was treated with topical sirolimus, resulting in decreased size and pain and improvement in motor function of his hand. This case demonstrates the efficacy of topical sirolimus in the management of neurofibromas in NF1.     

Successful treatment of isolated venous malformation with 1444-nm fiberoptic Nd-YAG laser

Two patients with isolated venous malformations on the face were treated with fiberoptic Nd-YAG laser (Lutronic laser company, South Korea). After nerve block anesthesia, the laser tip was pushed into the lesions either through a hole made by a 16 gauge needle or directly by inserting and triggering the laser tip few millimeters away from the lesions. The laser tip was pushed from one or few directions and moved back and forth, while triggering, in a fan pattern to cover the whole lesion. The procedure was continued till complete flattening of the lesions. The parameters used were pulse rate = 30 hertz, pulse energy = 300 mJoules, power = 6.0 watt, and total energy used for the first patient was 1000 Joules and for the second patient was 800 joules. Results: The lesions flattened completely after whole tissue coagulation. Moderate redness disappeared in the first 48 hours. No persistent discoloration and no sign of cutaneous burning appeared after the procedures. No antibiotic or analgesic was prescribed after the procedure. The patients were followed for more than 2 years with no recurrence and good cosmetic results. Conclusion: The fiberoptic Nd-YAG laser can be used as an effective procedure for venous malformations.     

D-penicillamine-induced pemphigus successfully treated with combination therapy of mizoribine and prednisolone

A 63-year-old woman had D-penicillamine-induced pemphigus with a high index value of circulating autoantibodies against desmoglein 1. Because of the lack of response to prednisolone monotherapy, the patient was treated with a combination therapy of mizoribine and low-dose prednisolone. The skin eruption was improved by this combination with a declined value of circulating anti-desmoglein 1 antibody. Currently, a remission of 2 months has been achieved, and prednisolone could be tapered.     

Intense pulsed light therapy (IPL) induced iritis following treatment for a medial canthal capillary malformation

The popularity of intense pulsed light (IPL) therapy continues to increase due to its relative safety, high skin coverage rate and ability to treat both vascular and pigmented lesions. An often‐overlooked risk is the potential for IPL‐induced ocular damage. The damage sustained can cause significant, persistent morbidity and can occur even with very limited IPL exposure to the eye.