piperidines and Pemphigus

Pemphigus is a rare autoimmune disease, which could be fatal without treatment. Recently, target therapy is increasingly being used in different autoimmune diseases. However, there are limited studies associated with target therapy in pemphigus. In this study, it was tried to identify the role of interleukin (IL) -21 in patients with pemphigus. Based on the available studies on the role of IL-21 associated with several cells, including T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells as well as regulatory B cells and regulatory T cells, the possible roles of this cytokine in pemphigus were discussed in detail. It was found that IL-21 is a crucial cytokine associated with pemphigus disease, which has not been discussed in this disease yet. It is able to promote T helper (Th) 2, Th17, T follicular helper (Tfh), CD8+ cytotoxic T lymphocytes (CTLs), NK and NKT cells. It also causes the production of immunoglobulin (Ig)G in addition to the decrease of Tregs. All the mentioned alterations seem to be involved in disease progression via different signaling pathways. Inhibition of these changes must cause improvement of disease severity. By inhibition of IL-21 or its receptor, it is expected that patients with severe pemphigus experience relative and gradual improvement. This inhibition could be induced by tofacitinib, which was approved by the US Food and Drug Administration as a treatment for rheumatoid arthritis patients, or anti-IL-21 monoclonal antibody, NNC114-0006. However, more studies are needed to confirm it as a promising therapy.

Topics: Animals; Antibodies, Monoclonal; Humans; Immunity, Cellular; Interleukins; Molecular Targeted Therapy; Pemphigus; Piperidines; Pyrimidines; Pyrroles

Paraneoplastic pemphigus (PNP) is a severe autoimmune blistering disease associated with an underlying malignancy, and its prognosis is poor. We herein report the first patient with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL)-associated PNP successfully treated with the Bruton's tyrosine kinase inhibitor ibrutinib and rituximab. Although his PNP lesions did not improve with ibrutinib monotherapy, the combination of ibrutinib and rituximab was effective against B-CLL/SLL-associated PNP. This case suggests that ibrutinib plus rituximab may be a potent therapeutic option for B-CLL/SLL-associated PNP that is hard to control with ibrutinib alone.

Topics: Adenine; Antineoplastic Agents, Immunological; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Paraneoplastic Syndromes; Pemphigus; Piperidines; Prognosis; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Rituximab; Treatment Outcome

Pemphigus is a rare, but life-threatening autoimmune disease with a high rate of morbidity and mortality, if left untreated. After the development of corticosteroid therapy in the 1950s, the death rate for pemphigus has significantly decreased. However, finding more potent therapeutic options for refractory patients has remained a controversial topic. In the recent years, rituximab has increasingly been used for the treatment of refractory pemphigus, but some patients do not well-respond. In addition, there is a paucity of evidence to support the risk of diseases exacerbation after rituximab therapy. In this study, as a JAK1 and JAK3 inhibitor, tofacitinib has been proposed for the treatment of refractory pemphigus patients.

Topics: Cytokines; Humans; Janus Kinase 1; Janus Kinase 2; Janus Kinase 3; Janus Kinases; Pemphigus; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Signal Transduction; Th2 Cells

We present the case of a 51-year-old man who developed paraneoplastic pemphigus (PNP) in the context of chronic lymphocytic leukemia (CLL). His CLL was successfully controlled with ibrutinib. Concurrently, there was significant improvement of his PNP, suggesting that ibrutinib may be a very useful addition to the treatment options in this potentially life-threatening autoimmune disorder.

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Paraneoplastic Syndromes; Pemphigus; Piperidines; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines