Dermatology: Practical and Conceptual


Dermatology Practical & Conceptual

Letter  |  Dermatol Pract Concept. 2021; 11(3): e2021029 1

Serum Sickness-Like Reaction: Drug-Induced 
Cutaneous Disease in a Child

Ana Carolina Galvão dos Santos de Araujo1, Liana Moura de Almeida1, Ana Paula Moura de 
Almeida1, Elisa Fontenelle de Oliveira2, Mayra Carrijo Rochael3, Rodrigo Aires de Morais4, Hudson 

Dutra Rezende1

1 Álvaro Alvim School Hospital. Department of Dermatology. Campos dos Goytacazes, Rio de Janeiro, Brazil.

2 Fernandes Figueira Institute/FIOCRUZ. Department of Pediatric Dermatology. Rio de Janeiro, Rio de Janeiro, Brazil.

3 Fluminense Federal University. Department of Pathology. Niterói, Rio de Janeiro, Brazil.

4 Campos dos Goytacazes, Rio de Janeiro, Brazil.

Key Words: Serum Sickness, Drug Hypersensitivity, Allergic Reaction, Anti-Bacterial Agents, Clavulanic Acid.

Citation: Galvão dos Santos de Araujo AC, Moura de Almeida L, Moura de Almeida AP, Fontenelle de Oliveira E, Carrijo Rochael M, Aires 
de Morais R, Rezende HD. Serum Sickness-Like Reaction: Drug-Induced Cutaneous Disease in a Child. Dermatol Pract Concept. 2021; 
11(3): e2021029. DOI: https://doi.org/10.5826/dpc.1103a29

Accepted: October 22, 2020; Published: July 8, 2021

Copyright: ©2021 Galvão dos Santos de Araujo et al. This is an open-access article distributed under the terms of the Creative Commons 
Attribution License BY-NC-4.0, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided 
the original authors and source are credited.

Funding: None.

Competing interests: The authors have no conflicts of interest to disclose.

Authorship: All authors have contributed significantly to this publication

Corresponding author: Ana Carolina Galvão dos Santos de Araujo, Álvaro Alvim School Hospital. Dermatology Department. Campos dos 
Goytacazes, Rio de Janeiro, Brazil. Email: anacarolinagsa@yahoo.com.br

Introduction

Serum sickness is defined as a type III hypersensitivity reac-

tion, which leads to complement activation and hypocomple-

mentemia, small vessel vasculitis, and nephropathy. From a 

clinical perspective it resembles Serum Sickness-Like Reaction 

(SSLR), presenting clinical similar findings. These are both 

rare diseases that can manifest with urticarial rash, fever, 

and arthralgia, mainly differing by their etiopathology and 

laboratory findings [1,2]. SSLR pathogenesis remains unclear 

but is probably related to an inflammatory response to drug 

metabolites, more commonly, following beta-lactams use. It 

is not mediated by immunocomplexes and does not manifest 

hypocomplementemia [1,2] .

Case Report 

An 18-month-old girl, presented with spread, non-pruritic, 

erythematous-edematous plaques (some violaceous) char-

acterized by irregular borders (Figure 1A). 2 days after, a 

violaceous inner halo appeared on the plaques and the patient 

developed systemic symptoms, including joint edema, arthral-

gia, limited mobility, irritability, hyporexia, and fever (Figure 

1B and 2). The patient had previously received oral amoxicil-

lin/clavulanate and dipyrone treatment 5 days before the skin 

lesions appeared, due to cough and fever. Oral prednisone 

0,5mg/kg and hydroxyzine did not help fade the lesions and 

following further clinical deterioration the situation worsened 

until she was admitted at the Intensive Care Unit (ICU).



2 Letter  |  Dermatol Pract Concept. 2021; 11(3): e2021029

Figure 1. (A)Diffuse erythematous and violaceous, edematous plaques on trunk, axillary region, and face. (B) After 2 days, 

appearance internal violaceous halo.

Figure 2. Diffuse arcuate and annular pink edematous plaques with 

central purple annular patches surrounding a yellowish center.

On the first day of hospitalization leukocytosis was at 

24.730/mm³, after 2 days it raised to 31.800/mm³; C reac-

tive protein analysis increased from 29,9mg/dL on the first 

day, to 90,2 mg/dL. Liver enzymes and renal function were 

normal. Transthoracic echocardiogram did not demonstrate 

any abnormality.

A skin biopsy was performed, and the histopathology 

showed normal epidermis, perivascular, periadnexal, and inter-

stitial inflammatory infiltrate, consisting of lymphocytes, neu-

trophils and numerous eosinophils, in addition to edema, with-

out vasculitis (Figure 3). Antibiotic treatment was suspended, 

antipyretic and oral corticosteroids (0,5 mg/kg/day) were main-

tained, in addition to venous hydration. After 3 days of hospi-

talization, she was discharged with significant improvement.

Conclusions 

Diagnosis of SSLR is clinical and can be made when annular, 

erythematous edematous plaques, similar to an urticarial reac-

tion, usually turning violet, giving the lesion an ecchymotic 

aspect, appear combined with systemic symptoms, such as 

arthralgia/arthritis, lymphadenopathy, malaise, and fever, fol-

lowing 8 to 14 days of drug exposure. SSLR diagnosis, needs 

however to be distinguished from other, potentially more seri-

ous conditions such as Lyme disease, endocarditis, erythema 

Figure 3. (H&E, x100) (magnification x400) Normal epidermis, 

and perivascular, periadnexal and interstitial cell infiltrate inflam-

matory infiltrate, consisting of lymphocytes, neutrophils and eosin-

ophils, in addition to edema without vasculitis.



Letter  |  Dermatol Pract Concept. 2021; 11(3): e2021029 3

multiforme, Kawasaki’s disease, and in some rare situations to 

neoplastic diseases. In this case, one of the first hypotheses con-

sidered before the dermatology evaluation, was meningococ-

cemia, and the patient almost underwent a lumbar puncture.

The treatment involves the discontinuation of the culprit 

drug and, if necessary, the use of corticosteroids, anti-inflamma-

tory, antihistamines, or sometimes, intravenous gamma globulin 

administration [1,2]. Early recognition of this condition leads to 

less family anxiety and a non-iatrogenic management, avoiding 

unnecessary and potentially harmful prescriptions [1,2].

References

1. Barreira P, Gomes E. Serum sickness -like reaction associated 

with drugs intake in pediatric age. Rev Port Imunoalergologia. 

2013;21(4):267–74. 

2. Yorulmaz A, Akın F, Sert A, Ağır MA, Yılmaz R, Arslan Ş. 
 Demographic and clinical characteristics of patients with serum 

sickness-like reaction. Clinical Rheumatology. 2018;37(5):1389–

94. DOI: 10.1007/s10067-017-3777-4. PMID: 28795234