tacrolimus and Paraneoplastic-Syndromes

Inflammatory mucosal disorders are treated conventionally with potent or superpotent topical corticosteroids. For more than 20 years, topical cyclosporine has been used in the management of oral mucous membrane affections. Recently other topically applied calcineurin inhibitors, namely tacrolimus and pimecrolimus, expanded the armamentarium for the treatment of inflammatory mucosal diseases. This chapter places its main emphasis on the efficacy and safety of topical calcineurin inhibitors in the management of different oral and genital conditions, including anogenital lichen sclerosus (LS), oral and genital lichen planus, plasma cell balanitis and vulvitis, mucous membrane pemphigoid and pemphigus vulgaris, all conditions having usually a protracted course, requiring long-lasting treatment. There is current evidence for the effectiveness of both pimecrolimus and tacrolimus in the topical treatment of inflammatory oral mucosal diseases and genital dermatoses, especially oral lichen planus and genital LS.

Topics: Administration, Topical; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Balanitis; Calcineurin Inhibitors; Carcinogens; Female; Genital Diseases, Female; Humans; Lichen Planus; Lichen Planus, Oral; Lichen Sclerosus et Atrophicus; Male; Mucositis; Paraneoplastic Syndromes; Pemphigoid, Benign Mucous Membrane; Pemphigus; Tacrolimus; Vulvitis

Inflammatory myopathies are chronic, immune-mediated diseases characterized with progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The aims of therapy are to increase muscle strength, prevent the development of contractures, and to manage the systemic manifestations of the disease. This is a complex treatment which requires routine and wide knowledge. The most important task is to recognize the disease and guide the patient to immunologic center. Although the first line of therapy continues to include corticosteroids, there are a multitude of agents available for treating patients with myositis. There are several different immunosuppressive agents which may be applied alone or in combination with each other, as well as an increasing number of novel and exciting biologic agents targeting molecules participating in the pathogenesis of inflammatory myopathy. Physiotherapy and rehabilitation in the remission period may significantly improve the functional outcome of patients with these disorders.

Topics: Adrenal Cortex Hormones; Algorithms; Antineoplastic Agents; Azathioprine; Biological Therapy; Cell Movement; Cyclophosphamide; Cyclosporine; Dermatomyositis; Exercise Therapy; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Paraneoplastic Syndromes; Physical Therapy Modalities; Polymyositis; T-Lymphocytes; Tacrolimus

Paraneoplastic pemphigus (PNP) or paraneoplastic autoimmune multiorgan syndrome (PAMS) is a life-threatening autoimmune blistering disease commonly associated with lymphoproliferative neoplasms. This article focuses on current management strategies in PNP/PAMS, and reported instances of their treatment successes and failures. Due to the rarity of the condition and the high rates of treatment failure, no randomized control trials exist to guide the evidence-based treatment of this condition; all evidence to date on the efficacy of therapeutic modalities has been gained from individual case reports, small case series, and expert recommendations.

Topics: Adrenal Cortex Hormones; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Autoimmune Diseases; Azathioprine; Cyclophosphamide; Cyclosporine; Dermatologic Agents; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Multiple Organ Failure; Mycophenolic Acid; Paraneoplastic Syndromes; Pemphigus; Plasmapheresis; Rituximab; Tacrolimus

A 75-year-old man visited our Collagen Disease Department because of a fever, edema in the lower legs, and arthralgia. He presented with peripheral arthritis of the extremities and was negative for rheumatoid factor, leading to a diagnosis of RS3PE syndrome. A search for malignancy was performed, but no obvious malignant findings were found. After starting treatment with steroid, methotrexate, and tacrolimus, the patient's joint symptoms improved, but after five months, enlarged lymph nodes throughout the body were observed. A lymph node biopsy revealed a diagnosis of other iatrogenic immunodeficiency-associated lymphoproliferative disorders/angioimmunoblastic T-cell lymphoma (OI-LPD/AITL). After discontinuation of methotrexate and follow-up, no lymph node shrinkage was observed, and the patient had strong general malaise, so chemotherapy was started for AITL. After the start of chemotherapy, the patient's general symptoms improved quickly. RS3PE syndrome is a polyarticular, rheumatoid factor-negative, polyarticular synovitis with symmetric dorsolateral hand-palmar symmetric indentation edema that occurs mainly in elderly patients. It is also noted as a paraneoplastic syndrome, with 10%-40% of patients having malignant tumors. When our patient was diagnosed with RS3PE syndrome, a search for malignancy was performed, but there were no findings suggestive of malignant disease. However, after methotrexate and tacrolimus administration was started, the patient developed rapid lymph node enlargement, and the pathology showed AITL. The possibility of AITL as an underlying disease and RS3PE syndrome as a paraneoplastic syndrome, or conversely, OI-LPD/AITL associated with immunosuppressive therapy for RS3PE syndrome is considered. We herein report this case, as sufficient recognition is required for a proper diagnosis to be made and treatment of RS3PE syndrome to be performed.

Topics: Aged; Edema; Humans; Immunoblastic Lymphadenopathy; Immunosuppression Therapy; Lymphoma, T-Cell; Male; Methotrexate; Paraneoplastic Syndromes; Rheumatoid Factor; Tacrolimus

Topics: Administration, Topical; Blepharitis; Chloroquine; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Injections, Intravenous; Middle Aged; Paraneoplastic Syndromes; Tacrolimus; Treatment Outcome

Topics: Female; Humans; Immunosuppressive Agents; Middle Aged; Paraneoplastic Syndromes; Pemphigus; Recurrence; Stomatitis; Tacrolimus