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.