Investigating the Efficacy Variability of Different JAK Inhibitors in Chronic Nonbacterial Osteitis (CNO) Presenting Primarily With Pyoderma Gangrenosum

Abstract

Chronic nonbacterial osteitis (CNO) represents an infrequent, chronic, and relapsing inflammatory affliction of the bone with an undetermined cause. It is distinguished by a persistent state of inflammation within the bone marrow, a condition that is not instigated by bacterial infections [1]. Necrobiosis gangrenosum, a rare inflammatory skin disease within the spectrum of neutrophilic dermatoses, is primarily characterized by painful ulcers [2]. In some instances, CNO may manifest in the form of pyoderma gangrenosum. This is predominantly attributable to the nature of CNO as an autoinflammatory disorder [1]. Previous studies have demonstrated the efficacy of Janus kinase inhibitors (JAKis) in the treatment of necrobiosis gangrenosum [2]. Here, we report a case of CNO predominantly manifested by necrobiosis gangrenosum, which showed significant improvement following treatment with abrocitinib.

The patient is a middle-aged male presenting with extensive skin rashes on the hands and trunk (Figure 1A1,A3), accompanied by pain in the upper chest and buttocks. Laboratory tests revealed a C-reactive protein (CRP) level of 17.8 mg/L, while a 99mTc bone image showed localized increased metabolic activity in the sternum and sacrococcygeal region (Figure 1B). Skin pathology confirmed the diagnosis of necrobiosis gangrenosum (Figure 1C), leading to a final diagnosis of CNO. The patient was initially treated with a nonsteroidal anti-inflammatory drug (NSAID) in combination with tofacitinib at a dosage of 5 mg twice daily for a duration of 6 months. Although there was relief from bone pain, the skin rash did not improve. Subsequently, the treatment regimen was changed to abrocitinib at a dosage of 200 mg once daily. After 6 months of this therapy, there was a marked improvement in the skin rash (Figure 1A2,A4).

Currently, JAKis have been widely utilized in treating SAPHO syndrome, consistently demonstrating favorable therapeutic outcomes [3]. Given that SAPHO syndrome's osteomyelitis is part of the CNO spectrum, we postulate that JAKis may also have comparable therapeutic effectiveness in treating CNO. Regarding the treatment of pyoderma gangrenosum, JAKis are regarded as a promising alternative therapeutic approach [4]. However, conventional literature suggests that abrocitinib can effectively treat pyoderma gangrenosum [5]. Against this backdrop, we commenced treating a patient with abrocitinib at a dosage of 200 mg once daily. After 3 months, a marked improvement was observed in the rashes on the patient's hands and trunk. After an additional 6 months of treatment, the skin lesions on the trunk showed even more significant alleviation compared to earlier evaluations. These results highlight the substantial advantage of abrocitinib in managing the skin manifestations of CNO, especially when pyoderma gangrenosum is the predominant feature. However, it is crucial to note that this is a single case report, and the limited duration of observation makes it impossible to determine whether abrocitinib can ensure sustained efficacy. Thus, continuous follow-ups and additional clinical studies are essential to validate the findings of this case report.

Ruitian Ma and Zhi Ye: drafted the manuscript; Ruitian Ma: responsible for data collection of patient samples and clinical information; Zhi Ye: was in charge of patient related picture sorting and editing; Chen Li: critically revised the manuscript for important intellectual content; Zhenhua Ying: supervised the whole research process.

The authors declare no conflicts of interest.