Case Study: RA Patient Develops Rare Reaction Related to Biologic Treatment

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This month: A noteworthy case study

What caused an older man with rheumatoid arthritis (RA) to develop a persistent fever? That's what Hiroaki Nishioka, MD, of Kobe City Medical Center General Hospital in Japan, and colleagues needed to determine.

As the authors detailed in BMJ Case Reports, when the patient presented to the hospital outpatient department, he told clinicians that the fever had developed 5 days previously. In addition to the RA, his medical history included chronic obstructive lung disease, high blood pressure, and diabetes mellitus.

He was taking numerous treatments for his RA, including prednisolone, salazosulfapyridine, and tacrolimus. He had also been receiving treatment with tiotropium bromide inhalant, amlodipine, and mitiglinide for the other conditions. Six weeks earlier, however, he had received his first injection of the biologic abatacept (Orencia), which was then followed by weekly doses.

Physical examination found that the patient's temperature was 38°C (about 100.4°F) and that there were small (<5 cm in diameter), poorly demarcated raised red lesions on his chest and back.

Lab tests revealed a white blood cell count of 15.5 × 10⁹ and a C reactive protein level of 22.3 mg/dL. Findings were negative for anti-nuclear, anti-Sjogren's syndrome-A and -B and anti- double-stranded DNA antibodies. Two sets of blood cultures did not yield any bacterial growth.

Nishioka and co-authors reported that ultrasound showed hyperechoic areas in the subcutaneous adipose tissue underlying the erythematous region. Biopsies of the erythematous lesions showed evidence of diffuse inflammatory infiltrates in the lobules of the adipose tissue, composed mainly of neutrophils. The elastic fibers of the vessels were preserved.

These findings suggested a diagnosis of panniculitis (inflammation of the subcutaneous fat) without vasculitis, the case authors determined.

The team discontinued treatment with abatacept injections and started the patient on colchicine 1.5 mg/day. Three days later, his temperature had returned to normal, and the skin lesions had cleared. Treatment was continued with colchicine for 14 days, but abatacept injections were not resumed.

Based on the clinical and histological findings, Nishioka and colleagues made a diagnosis of abatacept-associated panniculitis. This was supported by the patient's score of 7 on the Naranjo adverse drug reaction probability scale, which indicated a probable relationship between the symptoms and adverse drug reactions to abatacept.

Discussion

The authors explained that the biologic agent abatacept is used widely and worldwide in the treatment of RA, helping to reduce pain and joint inflammation by modulating the co-stimulatory signals involved in T-cell activation.

Although abatacept has been associated with a range of adverse reactions involving the skin, including cutaneous eruptions, urticaria, and psoriasis, only a few cases of panniculitis have been reported in patients taking the agent.

One reported case the team cited involved a patient who presented with lupus erythematosus panniculitis and another was a case of panniculitis with necrobiosis lipoidica-like features.

The present case, however, Nishioka and co-authors noted, "was characterized by demonstrated lobular panniculitis accompanied by neutrophil infiltration without vasculitis." This histological pattern has been seen in several panniculitis conditions – pancreatic panniculitis, alpha-1 antitrypsin deficiency panniculitis, traumatic panniculitis, and infectious panniculitis -- but their own patient's symptomatic course was not suggestive of any of these conditions.

Ultrasound of subcutaneous panniculitis often shows thickening of the fat tissue beneath the skin and "hyperechoic areas with poorly defined margin in the fat tissue," the team explained. Such imaging observations, however, are nonspecific and not helpful in distinguishing panniculitis from other conditions.

The authors noted that as a medication adverse effect, panniculitis rarely occurs in association with biologic treatments, but tends to occur most commonly in patients taking "oral contraceptives, nonsteroidal anti-inflammatory drugs, antibiotics, and leukotriene-modifying agents." This case showed, however, that abatacept can indeed rarely be associated with panniculitis, the team said.

This possibility should therefore be considered in the differential diagnosis when clinicians are presented with patients who develop fever and erythema after taking the biologic, Nishioka and co-authors concluded. They added that reports of additional cases may help to clarify the histological pattern of abatacept-associated panniculitis, which to date, remains poorly defined.