RS3PE was considered a symmetrical entity until Pariser and Canoso [4
] reported two cases of unilateral RS3PE. Both patients had neurological deficit, as case 1 has Erb's palsy, and case 2 was a known case of stroke with left hemiplegia. RS3PE occurred at the extremity that was spared. Later Finnell and Cuesta [5
] reported asymmetrical involvement of lower limbs in his case series with greater involvement of right lower limb in case 2. Keenan et al. [6
] later reported a case of right hemiplegic patient presenting with left sided RS3PE. Three more cases [7
] including two left sided and one right sided were also reported. The majority of them were associated with neurological disturbances, and association with rheumatoid arthritis or any other autoimmune disease was not shown in any of them.
The mechanism which leads to genesis of RS3PE is still under dark, but a high prevalence of unilateral RS3PE in patients with neurological deficits (central as well as peripheral) raises the suspicion that local and neurological factors play a role in pathogenesis and progression of disease. Animal studies have shown that inflammatory and joint destructive response is decreased on the side of neurological impairment [10
]. This is supported clinically by occurrence of unilateral disease on the side contralateral to side of neurological deficit. Role of vascular endothelial growth factor in pathogenesis of RS3PE is well established [11
]. Animal models suggested that in neurological injuries there is downregulation of VEGF receptors [12
]. Thus the neurological affected site may be resistant to development of edema. However, presence of unilateral disease in patients with autoimmune diseases is area still unexploited and needs more research which could establish the pathogenesis.
Previously Özşahin et al. [13
] reported a case of unilateral RS3PE that occurs in a patient of long-standing rheumatoid arthritis who was started on DMARDs but later left them, as his symptoms were not controlled. RS3PE developed three years after leaving the drugs. On the contrary, in our case symptoms were well controlled with DMARDs, and patient developed RS3PE when she was on medication. To the best of our knowledge, this is the first case of unilateral RS3PE in a patient of rheumatoid arthritis, while on drugs. This case also adds to clinical aspect according to which RS3PE is considered as a distinct clinical entity than rheumatoid arthritis as RS3PE occurred in a patient regularly taking DMARD.
To conclude, lack of specific diagnostic criteria and an asymmetrical unilateral pattern always poses diagnosis of RS3PE as a challenge. However, the diagnosis must be kept whenever a patients presents with acute onset polyarthritis with pitting edema on the back of extremity and a negative rheumatoid factor. Though the disease is rare in comparison to other common rheumatologic disorders as rheumatoid arthritis, it has an excellent prognosis. Misdiagnosis not only increases the duration of pain in the patient, but it also puts them on heavy cost of drugs.