sirolimus and Lymphatic-Diseases

Castleman disease is a rare hematologic disorder, closely linked to the HHV-8, and most commonly observed in immunocompromised individuals. Thirteen months following a liver transplant for CPS-1 defect, a 15-month-old boy presented with fevers, anemia, and growth retardation. Abdominal CT scan showed splenomegaly and generalized lymphadenopathy. Histology of chest wall lymph nodes revealed a mixed CD3+ T-cell and CD20+ B-cell population with atretic germinal centers consistent with multicentric Castleman disease. Qualitative DNA PCR detected HHV-8 in the resected lymph node and in the blood, supporting the diagnosis. Immunosuppression was tapered, and he was transitioned from tacrolimus to sirolimus. His graft function remained stable, and repeat imaging showed regression of the lymphadenopathy. The child is living one yr after Castleman disease diagnosis with a well-functioning graft. Castleman disease is a potential complication of solid organ transplant and HHV-8 infection. Reduction in immunosuppression and switch to sirolimus may be an effective strategy to treat this condition.

Topics: Adolescent; Adult; Antigens, CD20; B-Lymphocytes; Castleman Disease; CD3 Complex; Graft Survival; Herpesvirus 8, Human; Humans; Immunosuppressive Agents; Infant, Newborn; Liver Failure; Liver Transplantation; Lymphatic Diseases; Male; Middle Aged; Polymerase Chain Reaction; Sirolimus; Splenomegaly; T-Lymphocytes; Tacrolimus; Tomography, X-Ray Computed

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of disrupted lymphocyte homeostasis, resulting from mutations in the Fas apoptotic pathway. Clinical manifestations include lymphadenopathy, splenomegaly, and autoimmune cytopenias. A number of new insights have improved the understanding of the genetics and biology of ALPS. These will be discussed in this review.. A number of key observations have been made recently that better define the pathophysiology of ALPS, including the characterization of somatic FAS variant ALPS, the identification of haploinsufficiency as a mechanism of decreased Fas expression, and the description of multiple genetic hits in FAS in some families that may explain the variable penetrance of the disease. In addition, ALPS has been shown to be a more common condition, as patients diagnosed with other disorders, including Evans syndrome and common variable immune deficiency, have been found to have ALPS. Finally, the treatment of the disease has changed as splenectomy and rituximab have been shown to have unexpected ALPS-specific toxicities, and mycophenolate mofetil and sirolimus have been demonstrated to have marked activity against the disease.. On the basis of novel advances, the diagnostic algorithm and recommended treatment for ALPS have changed significantly, improving quality of life for many patients.

Topics: Autoimmune Lymphoproliferative Syndrome; fas Receptor; Female; Germ-Line Mutation; Humans; Immunosuppressive Agents; Lymphatic Diseases; Male; Mycophenolic Acid; Signal Transduction; Sirolimus; Splenomegaly

CLAPO syndrome (Capillary vascular malformation of the lower lip, Lymphatic malformations of the head and neck, Asymmetry and Partial or generalized Overgrowth) is a nonfrequent pathology. This syndrome is characterized by the capillary malformation (CM) of the lower lip, a very important clinical sign when diagnosing CLAPO. The aim of our report is to demonstrate that rapamycin could be a reliable and safe targeted therapy in lymphatic malformations (LMs). This drug is useful in reducing the LM's size before final surgical treatment. The clinical and radiological evolution of a patient with CLAPO syndrome is reported in this article, before and after the treatment with rapamycin.

Topics: Administration, Oral; Arteriovenous Malformations; Humans; Immunosuppressive Agents; Infant, Newborn; Lymphatic Diseases; Male; Sirolimus; Treatment Outcome

The study of vascular anomalies is a rapidly progressing field in medicine. The development of new knowledge in the pathology and management of these disease processes are exemplified in the treatment of hemangiomas with propranolol and generalized lymphatic malformations with sirolimus. Central conducting lymphatic anomalies have traditionally been refractory to medical and surgical interventions. We report a case of a central conducting lymphatic anomaly that was responsive to sirolimus. A 14-year-old boy presented with chylothorax and chyluria with a lymphangiogram demonstrating abnormal lymphatic flow and reflux along the entire course of the central channels. Traditionally, medical management has been limited to somatostatin and low-fat diet with poor response and surgical interventions that are palliative. Sirolimus allows a new medical option that could improve management of this unresponsive population.

Topics: Adolescent; Humans; Lymphatic Diseases; Male; Remission Induction; Sirolimus

A common situation presented in any clinical facility is a woman with swelling and redness of the breast. Diagnosis upon suspicion is often mastitis or inflammatory breast cancer, which are popular and well-known diseases of the breast. However, there is one main differential diagnosis which has to be taken into consideration: lymphedema of the breast. Twenty patients with internal diseases presented in our Breast Care Unit over a 4-year period with breast-affecting lymphedema. The patients suffered from cardiac failure, nephrotic syndrome, liver failure, lymphadenopathy, and central vein occlusion. Additionally, we identified 5 patients with a history of organ transplantation and under immunosupressive medication with sirolimus or everolimus. These mTor inhibitors are known to have unwanted side effects such as unilateral or bilateral upper/lower extremity peripheral edema or facial/eyelid edema, but as we know, isolated lymphedema of the breast represents a previously unreported complication.

Topics: Adult; Aged; Aged, 80 and over; Breast; Diagnosis, Differential; Everolimus; Female; Heart Failure; Humans; Immunosuppressive Agents; Liver Failure; Lymphatic Diseases; Lymphedema; Middle Aged; Nephrotic Syndrome; Sirolimus; Tissue Transplantation; TOR Serine-Threonine Kinases; Vascular Diseases

Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of the immune system caused by inadequate induction of apoptosis via the Fas pathway, mainly characterized by generalized lymphadenopathy, splenomegaly, and autoimmune cytopenias, as well as increased risk of lymphoma. Although the clinical course of ALPS is highly variable, without treatment long-term prognosis is unsatisfactory for most patients. ALPS has been treated with most of the existing immunosuppressive agents, with variable success. We hereby present a case of a child with ALPS whose greatly enlarged lymph nodes rapidly regressed upon initiation of rapamycin, a novel potential therapeutic agent in the treatment of ALPS.

Topics: Autoimmune Diseases; Female; Humans; Immunosuppressive Agents; Infant; Lymph Nodes; Lymphatic Diseases; Lymphoproliferative Disorders; Remission Induction; Sirolimus