A 16-year-old girl is brought to the office due to a day of joint pain and pruritic rash. Two days ago, the patient completed a 10-day course of amoxicillin-clavulanate for an episode of otitis media. Temperature is 38.2 C (100.8 F). On examination, the patient has a blanchable, erythematous, urticarial rash on the hands and feet. There are no target lesions, and the lips and oral mucosae are not involved. Generalized lymphadenopathy is present. Multiple joints are tender but not swollen. Ear examination shows no residual disease. Laboratory studies show a normal complete blood count, comprehensive metabolic panel, and urinalysis. What is the most likely outcome of this patient's current condition?
Serum sickness & serum sickness–like reaction | ||
SS | SSLR | |
Common | Foreign proteins in antivenom, antitoxin, or monoclonal antibody | Medications, particularly cefaclor, penicillin & TMP-SMX |
Immune | High titer | Mild or none |
Complement | Extensive | Minimal or none |
Onset | 5-14 days after exposure | 5-14 days after exposure |
Fever | High | Low-grade |
Arthralgia | Yes | Yes |
Urticaria | Yes | Yes |
Resolution | Spontaneous | Spontaneous (discontinue drug if still receiving) |
SS = serum sickness; SSLR = serum sickness–like reaction; TMP-SMX = trimethoprim-sulfamethoxazole. | ||
This patient's fever, arthralgia, urticarial rash, and diffuse lymphadenopathy in the setting of recent beta-lactam therapy suggests serum sickness–like reaction (SSLR). Although SSLR and serum sickness (SS) share similar clinical presentations, the underlying triggers and mechanisms differ. SS is triggered by foreign proteins in antitoxins, antivenoms, or monoclonal antibodies; it is marked by the generation of high titer immune complexes, immune complex deposition in tissue, and significant complement activation. In contrast, SSLR is typically triggered by beta-lactam (eg, amoxicillin) or sulfa antibiotics; it is thought to be due to genetic deficiencies in eliminating the metabolic by-products of these medications, which leads to hapten-mediated cytotoxic T-cell injury or direct cytotoxicity.
SSLR is most common in children and usually presents 5-14 days after medication initiation. Most patients have a mildly pruritic urticarial rash that persists >24 hours. Significant multiarticular joint pain is usually present. Examination usually reveals pain with joint movement, but signs of arthritis (eg, joint warmth, swelling, erythema) are usually absent. Low grade fever and generalized lymphadenopathy often occur.
Symptoms of SS and SSLR resolve completely over several days as the medication is eliminated by the mononuclear phagocyte system (SS) or by metabolic pathways (SSLR). However, the inciting medication should be discontinued in those still taking it. Although future exposure may not cause recurrent symptoms, the drug should be avoided when possible.
(Choice A) Nephritogenic strains of group A Streptococcus can cause glomerulonephritis due to immune complex formation. Although arthralgia is common, patients will have abnormal urinalysis (eg, hematuria, casts). In addition, urticaria would be atypical.
(Choice B) Late Lyme disease can cause chronic, progressive arthritis. Although Lyme disease is associated with rash, arthralgia, and fever shortly after transmission, the rash is a spreading, target-shaped, annular lesion (erythema migrans). Urticarial rash and recent beta-lactam therapy make SSLR more likely.
(Choice D) Epstein-Barr virus can increase risk for malignancy (eg, lymphoma), and treatment with amoxicillin during acute infection often causes rash. However, the rash is usually generalized, diffuse, and maculopapular; urticarial rash and lack of pharyngitis would be atypical.
(Choice E) Spontaneous SSLR does not occur; SSLR and SS require recent exposure to medication, vaccine, or foreign protein antigens.
Educational objective:
Serum sickness–like reaction is usually triggered by antibiotic therapy (eg, penicillin, sulfa drugs). It typically occurs in children 5-14 days after medication initiation and presents with low-grade fever, urticarial rash, and arthralgia. Manifestations resolve completely as the medication is metabolized over days.