Discussion

Serum sickness is a delayed immune reaction characterized by fever, rash, arthralgias, lymphadenopathy, and polyarthritis. This condition is type III hypersensitivity reaction, caused by deposition of immune complexes8. The main etiology behind this is immune complex formation between human protein and non-human (heterologous) protein. Medications which consist of heterologous antigen as a component are the most common cause of it9. Streptokinase used as a thrombolytic agent has Serum Sickness which is a rare but significant side effect where patients present with mild to severe symptoms causing significant morbidity. Serum sickness can occur regardless of the dose or route of streptokinase administration, including intracoronary therapy5. Mohsenzadeh et al. (2020) found serum sickness to be prevalent in the Iranian population due to antibiotic use, especially penicillin and the cephalosporin group of drugs13. Streptokinase has been used in various cardiovascular problems including myocardial infarction, arrhythmia and valve stenosis7. Few studies have shown an association between serum sickness and streptokinase therapy in the 20th century. This is the first study to show the association in the 21st century. In this case, we present a 36-year-old female who had a significant history of mitral stenosis and underwent thrombolysis by streptokinase treatment presented with the complaints of fever and arthralgia for 3 days.  The correlation between detailed history and examination is required for suspected serum sickness. For the diagnosis, exposure of the offending agent within two weeks should be there, however in case of repeat exposure, within the few days before the presentation. The physical findings include arthralgia in the hands, feet, ankles, knees, and shoulders5. Rashes can also be present, which can be urticarial, maculopapular, or vasculitis eruption. The rashes might take weeks to resolve when the offending agent is resolved. Less commonly, there can be associated edema, lymphadenopathy, headache, and splenomegaly13. Our case presented with a history of streptokinase therapy within 2 weeks and presented with fever, arthralgia of bilateral knee joints.  To assess potential additional etiologies and multi-organ system involvement, the clinician ought to consider the subsequent laboratory tests: erythrocyte sedimentation rate, C-reactive protein, total hemolytic complement, C3, C4, basic metabolic panel, liver transaminases, antinuclear antibody, rheumatoid factor, and complete blood count with differential10. These findings suggest the role of immune complexes in pathophysiology of serum sickness. In our case as well, the patient had elevated ESR and CRP level suggesting infectious pathology, however renal function test, and urinalysis were normal. To rule out other rheumatological conditions, antinuclear antibody, ELISA, Direct Coombs, Rheumatic factor, Anti CCP, LDH tests were done and were negative. Treatment typically involves withdrawal of streptokinase, but systemic corticosteroids may be necessary in severe cases with end-organ damage11. In this case, the patient had symptoms of fever and arthralgia for 3 days which relieved on withdrawing the offending agent streptokinase. Though less common, early recognition and prompt treatment in severe cases is crucial otherwise it will lead to morbidity of the patient12. The prognosis of serum sickness is quite good and used to resolve within 1-2 weeks if the offending agent is discontinued. However, repeated exposure to a causative agent have also led to renal failure and even death5.