Rare Inflammatory Arthritis, Still’s Disease, Is Potential aHUS Trigger, Case Report Suggests

A rare type of inflammatory arthritis known as Still’s disease may trigger the development of atypical hemolytic uremic syndrome (aHUS), a recent case report suggests. A timely diagnosis of these conditions is critical to avoid irreparable damage to organs, the authors warn.

The report, “Aggressive Disease and Rare Sequelae in a Unique Case of Atypical Hemolytic Uremic Syndrome Secondary to Adult Onset Still’s Disease,” was published in the Journal of Hematology.

Still’s disease is a systemic inflammatory condition characterized by fever, rash, and joint pain. The cause and underlying biology of this condition is unclear. It typically is diagnosed by exclusion — that is, by ruling out other possible diagnoses.

aHUS is characterized by thrombotic microangiopathy (TMA), which is the formation of tiny clots in blood vessels. Generally, it is believed that aHUS develops in response to a particular “trigger,” such as an infection. Whether Still’s disease could serve as such a trigger is unclear, though aHUS has been reported previously in people with adult-onset Still’s disease (AOSD).

The new report describes the case of a 69-year-old woman who went to the hospital with symptoms that included fever, fatigue, impaired vision, joint pain, and a rash. Lab tests revealed high levels of inflammatory markers such as C-reactive protein, and a chest scan indicated lung damage.

A number of possible conditions — including lupus, sarcoidosis, and Sjogren’s syndrome, as well as infections — were ruled out through subsequent lab tests.

“Given her skin rash, pulmonary findings, and elevated inflammatory markers in the context of a negative infectious and autoimmune evaluation, the possibility of AOSD was considered,” the researchers wrote.

The patient was given glucocorticoids (a type of anti-inflammatory steroid) and was advised to see a primary care doctor for subsequent evaluation. However, a month later, the patient experienced a grand mal seizure (a seizure with loss of consciousness and violent muscle contractions) and was admitted to the emergency department.

Subsequent laboratory tests showed thrombocytopenia (low platelet count), and were indicative of microangiopathic hemolytic anemia (where red blood cells are destroyed due to damage from clots) and of kidney damage.

“Given her neurological symptoms, acute renal injury, microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, the overall picture was felt to be consistent with TMA,” the researchers wrote.

The patient was started on hemodialysis and plasma-exchange, which resulted in some improved symptoms, though kidney function remained poor. The patient was given Soliris (eculizumab) for managing TMA, as well as prednisone (an anti-inflammatory steroid drug) for the presumed AOSD. These resulted in further symptom improvement and the normalization of laboratory parameters.

Collectively, the patient’s symptoms and response to treatment were considered to be indicative of aHUS. More specifically, the case investigators proposed that, in this patient, aHUS likely was triggered by Still’s disease.

“Although the precise pathophysiological association between AOSD and TMA has yet to be defined, AOSD is known to result in profound systemic inflammation, and thus, undoubtedly, has the potential to generate robust activation of the alternate complement cascade [which causes aHUS],” they wrote.

This highlights the need for prompt diagnosis of Still’s disease. The researchers noted this patient had to wait months to receive a proper diagnosis, which delayed appropriate treatment and likely resulted in more severe disease developing.

“While AOSD is, for the most part, a diagnosis of exclusion, physicians should not allow the lack of a recognized disease association or definitive diagnosis to result in a critical delay in treating a very serious disease, which in severe cases, may result in significant morbidity and/or mortality,” the team concluded.