Historically axial spondyloarthritis (axSpA) was considered a male predominant disease. With the evolution of the concept of axial SpA over the last decade, it has been established that axSpA is common in females and is almost equal in distribution. However, axSpA in women is still underrecognized in daily clinics and research studies.

Challenges in early diagnosis of axial SpA in females

The significant delay in diagnosis of axSpA in females could be attributed to various socioeconomic and cultural factors in our society. Chronic back pain in females is often neglected by patients, families, or primary care physicians. Even when a young female reaches to primary care physician back pain is usually attributed to lifting heavy weights during daily activities, calcium/vitamin D deficiency, menstrual pain, etc.
The lack of knowledge of inflammatory back pain (IBP) at the primary care level also plays a part. The studies have shown that the prevalence of typical IBP is less in females than males, which also leads to missing early diagnosis of axSpA in females even by specialists. In my observation, classical IBP is not as frequent in women, maybe as they get moving and active early in the morning for chores and may experience earlier resolution of morning stiffness in mild disease. It also may be ignored by the patient instead of their widespread pain.

Differences in male and female axSpA: presentation and treatment response

The presence of the HLA B27 allele is less in females than in males. Females have longer disease duration, and more frequency of extra-articular manifestations like enthesitis, psoriasis, and IBD. The lifetime risk of anterior uveitis in axSpA in males and females is around 30%, however, as males are diagnosed with axSpA earlier than females, uveitis prevalence is also higher in them. The radiographic damage is less in females. Hip joints are less involved in females than males. The research has shown that in women axSpA disease starts as peripheral arthritis and enthesitis in contrary to males where back pain is a common primary symptom. Patient-reported disease outcomes like BASDAI, and quality of life indicators are higher in females. These could be explained by sex-related differences in pain mechanisms. Studies have shown that pregnancy doesn’t improve symptoms in axSpA. Pregnant axSpA patients tend to have variable disease activity over three trimesters and postpartum flares are noted. Males usually have higher CRP as an acute phase reactant, while ESR values are usually similar in males and females. The current evidence from multiple studies indicates a significantly lower efficacy, response rate, and drug survival for TNFis in female axSpA patients compared with male patients. Accurate interpretation of MRI findings is important to avoid overdiagnosis in females. Post-partum status, osteoporotic/osteomalacia fractures, anatomic variations, and mimics like osteitis condensans ilii should be considered while reporting MRI findings in females. Putting the pieces of the puzzle together including the history of chronic LBP with IBP, extra muscular manifestations, arthritis, inflammatory markers, and focused imaging read by experts will help in early diagnosis.
 

Suggested Readings

1. Wright GC, Kaine J, Deodhar A. Understanding differences between men and women with axial spondyloarthritis. Semin Arthritis Rheum.2020;50(4):687-694.
2. Marzo-Ortega H, Navarro-Compán V, Akar S, Kiltz U, Clark Z, Nikiphorou E. The impact of gender and sex on diagnosis, treatment outcomes and health-related quality of life in patients with axial spondyloarthritis. Clin Rheumatol.2022 ;41(11):3573-3581.