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Revista chilena de pediatría

Print version ISSN 0370-4106

Rev. chil. pediatr. vol.89 no.4 Santiago Aug. 2018 


Scarlet fever associated with hepatitis in pediatrics. A case report

Arvind V. PanchooA 

Miguel SapsB 

Edgardo D. Rivera RiveraB 

A Department of Pediatrics, Jackson Memorial Hospital, United states.

B Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Miami, Miller School of Medicine, United states.



La escarlatina es una enfermedad común en Pediatría, causada por Estreptococo beta hemolítico grupo A (SBHGA), la cual generalmente se presenta después de un episodio de faringitis, y con excelente pronóstico general. La hepatitis secundaria a escarlatina es una complicación, descrita muy rara vez en niños. Nuestro objetivo fue reportar la ocurrencia de hepatitis secundaria a escarlati na en un paciente pediátrico.

Caso Clínico:

Varón de 12 años cursando escarlatina, quien se presentó con una historia de 4 días de ictericia, coluria y disminución del apetito. Los exámenes de laboratorio revelaron elevación de las transaminasas y de los niveles de bilirrubina total y directa, y estudios vira les negativos para Hepatitis A, B y C, Virus de Epstein Barr, Parvovirus B19, Citomegalovirus, Virus Herpes 6 y Herpes simplex 1 y 2. Ecografía abdominal fue normal.


La hepatitis es una complicación inhabitual de la escarlatina, cuya patogénesis aún no está clara. La producción de citoquinas a través del daño celular mediado por la exotoxina pirógena estreptocócica, se ha propuesto como un posible mecanismo de hepatotoxicidad en infecciones por SBHGA.


La hepati tis asociada a escarlatina continúa siendo una entidad rara, pero de curso benigno, con recuperación plena en semanas a meses.

Palabras clave: Escarlatina; hepatitis; Estreptococo grupoA beta-hemolítico; pe diatría


Scarlet Fever is a common pediatric illness caused by group A beta hemolytic Streptococcus (GABHS), usually following an episode of pharyngitis1,2. Typi cally, it is characterized by fever, a red colored tongue and fine erythematous rash followed by desquama tion1,3. Rheumatic fever, glomerulonephritis, septic arthritis, osteomyelitis, pneumonia and otitis media are some of the well-documented complications of GABHS infection1,2. Nevertheless, with appropriate antibiotic treatment scarlet fever carries an overall excellent prognosis. Hepatitis secondary to scarlet fever is a rare complication described in adults and even less frequently in children2. Though the associa tion between scarlet fever and hepatitis was first reported in 1931, the pathogenesis still remains largely unknown, and there exist only few pediatrics cases in the literature highlighting the course, prognosis and eventual outcomes of these patients1-6. Herein, we report a pediatric case of scarlet fever associated with hepatitis, the first to the best of our knowledge in over fifty years in North America. The objective of this article is to raise awareness among pediatricians regarding possible hepatic involvement with scarlet fever.

Clinical case

A 12 year old male with recently diagnosed scar let fever presented to our institution with a four day history of jaundice, dark urine and decreased appetite. His illness began nine days prior to admission with fe ver and sore throat. On the third day he developed an erythematous, papular rash of the face, trunk and ex tremities. He was taken to an urgent care center where a rapid antigen test (throat swab) for group A Strep tococcus was found to be positive. Subsequently, the patient was diagnosed with scarlet fever and started on a five day course of amoxicillin.

In our emergency department, his vital signs were all stable and normal for age. Physical examination re vealed bilateral scleral icterus, fine, erythematous, pa pular rash over the face, trunk and extremities without abdominal tenderness, hepatomegaly or splenome galy. Initial laboratory evaluation was significant for hemoglobin of 11.8 g/dl [Reference Range 11 -16g/ dl], elevated white blood cells of 20,300/ml [Reference Range 4,500-13,000/ml] with a neutrophil predomi nance, normal electrolyte and renal function profile, elevated anti-streptolysine O (ASO) titer of 209 IU/ml [Reference Range < 200 IU/ml], elevated liver enzymes and elevated total and direct bilirubin levels (Table 1). Urinalysis was positive for bilirubinuria without proteinuria, hematuria or pyuria. Ultrasound exami nation of the liver, gallbladder and biliary system was unremarkable, with the spleen demonstrating normal echogenicity and size.

Table 1 Laboratory Parameters with Reference Ranges in Parenthesizes. 

At that point the Pediatric Gastroenterology service was consulted and further investigations were perfor med. These included antibody serology tests for he patitis viruses A, B and C, hepatitis B surface antigen, antinuclear antibody, DNA polymerase chain reaction (PCR) for Epstein Barr virus, parvovirus B19, adeno virus, cytomegalovirus, human herpes virus 6, herpes simplex virus 1 and herpes simplex virus 2. All of these resulted negative. Serum ceroplasmin and C3 and C4 complement levels were also sought and were found to be in the normal range.

The patient was provided with symptomatic care and by day eleven of illness his rash began to fade, and desquamation of the palms and soles was obser ved. He was discharged with good oral tolerance following a stable hospital course. At outpatient follow up three weeks later, he was asymptomatic with re solution of icterus and down trending liver enzymes (Table 1).


The incidence of hepatitis with scarlet fever in pe diatrics is not known, but by all accounts seems to be rare. Contributing to this uncertainty are published cases of hepatitis in scarlet fever without jaundice, lea ding some authors to believe that hepatitis may simply be missed or overlooked in scarlet fever without icterus3,5.

Girisch and Heinger on review of the literature no ted that hepatitis appears to closely follow the develo pment of the characteristic rash5. As in our case, the patient developed a fine erythematous, papular facial rash on day three of illness and then experienced onset of jaundice and dark urine on the sixth day, with eleva tions of liver enzymes discovered soon after.

Though first described by MacMahon and Ma llory in 1931, the pathogenesis of liver involvement in scarlet fever remains unclear4. In an autopsy series of fifty-nine cases of scarlet fever, post-mortem cultures of lung tissue and blood yielded growth of GABHS but those from liver tissue did not; arguing against direct bacterial hepatic injury1. However, streptococcal pyro genic exotoxin mediated cellular injury has been pro posed as a possible mechanism of hepatoxicity in GA- BHS infections. It is believed that such exotoxins have the ability to interact with both the major histocompa tibility complex molecules of antigen presenting cells and T-cell receptors, thereby acting as ‘super antigens’, with the end result of stimulating T cells to produce cytokines capable of inciting liver injury7.

It has been demonstrated that individuals pro duce varying degrees of cytokine responses to the same streptococcal super antigen. In that study, the investigators noted that patients with a propensity to produce higher levels of cytokines experienced more significant systemic manifestations than those who produce lower levels of cytokines in response to the same streptococcal super antigen8. Indeed, in prepa ring this report we came across two cases of hepatitis in scarlet fever associated with gallbladder hydrops; one even describing splenomegaly and ascites3,9. All of this is to say, that there may exist, a spectrum of scarlet fever disease presentation, possibly attributed to host factors affecting the level of lymphokine pro duction in response to GABHS infection, with scarlet fever associated hepatitis being on the more severe end of the range.

Patients presenting with a clinical picture of cho lestatic hepatitis in the setting of scarlet fever raises a number of etiological considerations. Leptospirosis for instance shares many similar features seen in our patient, namely; jaundice, fever, neutrophilic leuko cytosis and even various skin exanthemas has been observed in this disease process10. The absence of sig nificant abdominal tenderness, hepatomegaly, sple nomegaly, myalgia, headache, renal involvement and history of exposure to infected animals (dogs, rodents) makes this condition less likely. Bradycardia and high remittent fever have been described in association with leptospirosis10, none of which occurred during our patient’s disease course.

Many of the clinical features observed in this case can be attributed to Kawasaki disease and typhoid fe ver. Our patient described a four day history of inter mittent fever and never exhibited mucous membrane changes, bilateral conjunctival injection or cervical lymphadenopathy, hence his presentation did not meet the diagnostic criteria for complete Kawasaki di- sease11. Kawasaki disease can be associated with mild to moderate elevations of serum transaminases and hyperbilirubinemia but without objective evidence of at least five days of fever and other supplemental laboratory criteria such as pyruia and thrombocyto sis (platelet count > 500 x 103/microL), incomplete Kawasaki disease remains very unlikely12. Typhoid fever was essentially ruled out given the lack of cha racteristic salmon-colored spots on trunk and abdo men, bradycardia or travel to areas where this illness is endemic3.

Since our patient presented with cholestatic he patitis and received amoxicillin, some readers may question whether this may have been secondary to amoxicillin use. Hepatitis is a very rare occurrence with amoxicillin treatment, having a six fold higher incidence when a combination of amoxicillin and clavunate is used. Also, such reports describe older patients with longer durations of antibiotic use13. Our patient was prescribed a five day course of only amoxicillin.

Scarlet fever is diagnosed largely on clinical ma nifestations but in equivocal cases pharyngeal culture and ASO titers are followed14. ASO titers begin to rise after 1 week of illness and peaks in three to five weeks3. Given a history of fever, sore throat, characteristic rash with desquamation, a positive rapid antigen test for group A Streptococcus and elevated ASO titers the authors feel confident that this patient’s cholestatic hepatitis is associated with an initial presentation of scarlet fever.

At outpatient follow up, liver enzymes were no ted to have decreased significantly, though still mildly elevated from normal. Unfortunately the patient has defaulted from outpatient visits but has expressed to clinical staff the absence of jaundice, dark urine, pale stools and abdominal pain in a telephone interview four months post hospital discharge.

To the best of our knowledge, this report presents the first case of scarlet fever associated with hepatitis in over fifty years in North America. The last, described an 18 year old female admitted to a University Hospital in Maryland in 1962. Scarlet fever was diagnosed based on typical clinical symptoms and positive pharyngeal culture, with hepatitis noted on liver biopsy10. Since then other cases have been sporadically identified in various nationalities1-6,9,15,16.


Many healthcare providers, including general pe diatricians may not be aware of this entity, potentia lly leading to thorough investigation and a more pro longed hospital course that can significantly increase the cost of health care. With this case we aim to raise awareness among pediatricians regarding possible he patic involvement with scarlet fever and underline that such patients generally follow a benign disease course with complete recovery expected over several weeks to months.

Responsabilidades Éticas

Protección de personas y animales: Los autores decla ran que los procedimientos seguidos se conformaron a las normas éticas del comité de experimentación hu mana responsable y de acuerdo con la Asociación Mé dica Mundial y la Declaración de Helsinki.

Confidencialidad de los datos: Los autores declaran que han seguido los protocolos de su centro de trabajo sobre la publicación de datos de pacientes.

Derecho a la privacidad y consentimiento informa do: Los autores han obtenido el consentimiento informado de los pacientes y/o sujetos referidos en el artículo. Este documento obra en poder del autor de correspondencia.

Conflicto de intereses: Los autores declaran no tener conflicto de intereses.


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Recibido: 04 de Abril de 2018; Aprobado: 25 de Mayo de 2018

*Correspondencia: Arvind V. Panchoo

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