Patient Develops AAV Due to Familial Mediterranean Fever, Case Study Shows

Blood vessel inflammation caused by ANCA antibodies should be considered in the differential diagnosis of familial Mediterranean fever with hyperthyroidism, a case study shows.

The study, “Antineutrophil cytoplasmic antibody-positive familial Mediterranean fever and hyperthyroidism: A case report,” was published in the journal Medicine.

Familial Mediterranean fever (FMF) is a rare autoimmune disease characterized by painful inflammation of the membranes lining the abdomen and lungs, and of the joints, with recurrent episodes of high fever that last one to three days.

It is caused by a genetic mutation in the familial Mediterranean fever (MEFV) gene, which provides the instructions for making the pyrin protein. While believed to play a role in regulating inflammation, the role of pyrin is largely unknown.

In this study, Japanese researchers reported the case of a 41-year-old man with this rare condition, despite not having a family history of genetic disorders.

In 2014, the patient came to the hospital with complaints of upper and lower extremity motor disturbances. A clinical evaluation showed reduced nerve cell responsiveness, which led the clinical team to diagnose him as having polyneuropathy (nerve cell damage disease).

The man was taking Cozaar (losartan) and Norvasc (amlodipine) for his high blood pressure, and propylthiouracil for hyperthyroidism (overactive thyroid). In June 2017, however, the man was positive for ANCA antibodies.

Because long-term treatment with propylthiouracil is known to increase the risk for ANCA-associated vasculitis, the team suspected the treatment was causing the rise in ANCA antibodies and discontinued propylthiouracil. However, the numbness didn’t improve.

In late 2017, the patient again was admitted to the hospital with chest pain and high fever. He did not show signs of neurological, respiratory, or abdominal alterations, and muscle strength was normal.

Laboratory analysis at admission were suggestive of muscle damage and active inflammation. Also, ANCA antibody levels were still high.

A chest computed tomography (CT) revealed swollen lymph nodes and fluid build-up in the area surrounding the lungs, indicating active pleural inflammation. The symptoms led to a diagnosis of FMF, which was confirmed with genetic tests — the patient had a mutation in the MEFV gene.

The man started treatment with colchicine, which improved the numbness and lowered inflammation symptoms. Fever did not recur after treatment was started.

The researchers explain that while ANCA antibodies are used as a biomarker of ANCA-associated vasculitis, they also may be found in other diseases. In this case, investigators believe that a kind of extracellular network produced by immune cells as a defense mechanism against bacteria is overproduced in FMF, and this network leads to the formation of ANCA antibodies.

“The appearance of ANCA and vasculitis development should be considered in the clinical course of patients with FMF,” the researchers concluded.