Role of Sirolimus in Treatment of Microcystic , Mixed Lymphatic and Vascular Malformations

Role of Sirolimus in Treatment of Microcystic , Mixed Lymphatic and Vascular Malformations

Lympho-vascular malformations result from errors in embryologic vasculogenesis involving capillaries, veins, arteries, lymphatics, or a combination of these. Infantile haemangiomas & Vascular malformations like : Capillary malformations & Venous malformations : they increase in size and never regress on their own. & They are generally present at birth, they enlarge in response to infection, hormonal changes or trauma . Lymphatic malformations can be classified into macrocystic (cyst diameter >1cm), microcystic (cyst diameter <1 cm), or mixed , in macrocystic lymphatic malformations, surgery and sclerotherapy are effective . Surgery of microcystic lymphatic malformations remains challenging due to their infiltrative nature & Sclerotherapy is often impossible. As especially large microcystic and mixed malformations are still a therapeutic challenge, pharmaceutical treatment as sirolimus is used in last years as main line of treatment with great efficacy.

Lympho-vascular malformations result from errors in embryologic vasculogenesis involving capillaries, veins, arteries, lymphatics, or a combination of these. Infantile haemangiomas & Vascular malformations like : Capillary malformations & Venous malformations : they increase in size and never regress on their own. & They are generally present at birth, they enlarge in response to infection, hormonal changes or trauma . Lymphatic malformations can be classified into macrocystic (cyst diameter >1cm), microcystic (cyst diameter <1 cm), or mixed , in macrocystic lymphatic malformations, surgery and sclerotherapy are effective . Surgery of microcystic lymphatic malformations remains challenging due to their infiltrative nature & Sclerotherapy is often impossible. As especially large microcystic and mixed malformations are still a therapeutic challenge, pharmaceutical treatment as sirolimus is used in last years as main line of treatment with great efficacy. Sirolimus is a natural macrolide isolated from a bacteria strain of the Streptomyces genus & Streptomyces hygroscopicus . It was initially used as an antibiotic and antifungal agent, subsequent studies have revealed impressive cytostatic, antiproliferative, and immunosuppressive properties . Sirolimus not only prevents the growth of abnormal lymphatics but also induces the partial regression of lesions, without apparent effects on normal lymphatics .

Inclusion Criteria:

• from age 6 months to 12 years , not before 6 months to complete their vaccination program & maturation of hepatic enzymes .
• Patients diagnosed with microcystic & mixed Lymphatic malformations .
• After failure of other lines of treatment as regard propranolol , steroid for infantile haemangiomas & Vascular malformations and lymphovascular malformations .
• After failure of surgical excision & injection of bleomycin of Lympho-vascular malformations

Exclusion Criteria:

• Macrocystic Lymphatic malformations & high flow vascular malformations like arterio-venous malformations .
• An active infection that requires systemic treatment during the attack .
• Side effects of the drug as ( history of an allergic reaction to sirolimus or patients who develop severe allergic reaction to drug during treatment , hyperlipidemia , leucopenia , etc… )
• Chronic liver or kidney disease or on chronic drug treatment as (steroids, interferon or chemotherapeutic agents) .
• An immunodeficiency condition such as a human immunodeficiency viral infection or primary immunodeficiency disease.
• Patients who received drug less than 6 months duration .