# Severe Invasive Group A Streptococcal Disease with Rhabdomyolysis but without Evidence of Shock or Local Myositis

Authors: Arthur Okere; David Schwartz; Philip Tierno; Patrick Schlievert; Randa Hamadeh
Journal: Scholarly Research Exchange
 (2009)

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## Abstract

We report a presentation in an adult withStreptococcus pyogenes bacteremia and invasive tissue disease with rhabdomyolysis, but without evidence of toxic shock syndrome or local myonecrosis. We thus investigated how this infecting strain differed from strains known to cause toxic shock syndrome.


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## Body

## 1. Introduction

Severe invasive  group A streptococcal infections have been previously   described to cause  bacteremia, necrotizing fasciitis, gangrenous  myositis, pneumonia, or other possible syndromes associated with this organism being isolated from a usually sterile area of the body [1]. Group A streptococcal toxic shock syndrome (TSS) has been defined as a clinical syndrome characterized by hypotension (at the time of admission or within four to eight hours), as well as two or more signs of organ failure, such as liver or renal dysfunction, adult respiratory distress syndrome, erythematous macular rash, coagulopathy, or soft tissue necrosis [2]. We report a presentation in an adult with group A streptococcal bacteremia and other manifestations of toxic shock syndrome, however, not found to have the associated shock.


## 2. Case Report

A 41-year-old
male was  brought to the Emergency Room (ER) after having called 911 with
complaints of right ear pain and discharge, decreased hearing acuity, headache,
dizziness, and subjective fevers over the 3 days prior to admission. His past
medical history is only significant for heavy alcohol abuse,
methylenetetrahydrofolate reductase (MTHFR) deficiency with concomitant
hyperhomocysteinemia and multiple DVT/PEs. According to family members, he
experiences a baseline tremor in the upper extremities of unknown etiology,
unassociated with alcohol usage or withdrawal episodes. The patient admits to
having a young child who was recently treated forStreptococcus pyogenes pharyngitis. His only medication is daily Coumadin for his hypercoagulable state.
He denies alcohol consumption in the past week as well as any usage of IV
drugs.When seen in the
ER, he was observed to be alert and oriented, tremulous, febrile to103°F,
tachycardic and normotensive. Physical exam was only notable for serous discharge
from the right ear, warmth, erythema, and swelling of the right forearm, elbows
and knees, bilaterally. The examinations of his heart, lungs, and abdomen were
unremarkable; neurological exam was nonfocal. Laboratory tests initially
revealed serum creatinine of 1.2 mg/dL and transaminases of AST/ALT 152/65 U/L, total bilirubin 1.6 mg/dL,
conjugated 0.3, Hgb 14.6 g/dL, HCT 41.2%, platelet count 118×109/L, albumin 3.7 g/dL. Initial
urinalysis findings were a specific gravity 1.028, pH 5.5, small bilirubin,
trace ketones, protein >299, positive nitrites, small leukocyte esterase,
large blood, with 6–10 red blood cells, 3–10 white blood cells, urine cultures
with no growth.Laboratory tests
8 hours later revealed serum creatinine and transaminases of
1.6 mg/dL and
AST/ALT 1867/573 U/L respectively, as well as rhabdomyolysis with serum
creatine phosphokinase of 8030 U/L. His serum alcohol, serum and urine
toxicology screen were all negative. The patient, who had initially been
administered valium in the ER for presumed alcohol withdrawal, was later found
to be somnolent, and in respiratory distress requiring intubation. He was
admitted to the ICU for further monitoring, broad spectrum antibiotics, and
intravenous fluid management. A delayed lumbar puncture was performed a few
hours after antibiotics, with CSF revealing total protein
234 mg/dL, glucose 69 mg/dL, nucleated cells of 205/mm3, neutrophils 92%, lymphocytes 7%,
monocytes 1%, final CSF gram stain, and cultures being negative.During his stay
in the intensive care unit, he continued to have intermittent fevers. Admission
blood cultures were
positive forStreptococcus pyogenes, susceptible to penicillin. Blood
culture bottles were obtained using
the BacT/Alert 3D Blood Culture System,
Biomerieux, Inc., Durham, NC, USA. Antibiotic susceptibility was performed with Vitek Two, Biomerieux, Inc., St Louis, Mo, USA.
Antibiotics were later narrowed to penicillin G, with
clindamycin and 3 doses of IVIG administered in case of toxin production. Serum
creatine phosphokinase levels continued to rise daily, with concomitant liver
and renal dysfunction. Given the findings of warmth, erythema, and swelling of
the elbows and knees bilaterally, joint fluid was obtained from these sites
which also grew Streptococcus pyogenes. CT scans of the head was within
normal limits, and scans of the body/extremities resulted in no findings of
focal myositis. A transthoracic echocardiogram revealed no valvular
vegetations, and an ENT exam was
significant for otitis media. Lower extremity dopplers were also
obtained, which revealed no evidence for acute deep vein thrombosis.On hospital day
3, the patient remained intubated, however alert, neurologically nonfocal, and
responsive to commands. The patient remained intermittently febrile, however
hemodynamically stable, with  no significant drop in blood pressure since
admission. Serum creatine phosphokinase levels peaked at
139,781 U/L on
hospital day 4, with subsequent decline. After
serum AST/ALT values peaked at 3217/1046 U/L on hospital day
3, and serum creatinine 4.0 mg/dL on hospital day 6, hepatic and renal function
likewise improved. By hospital day 7, the patient underwent successful
extubation, and was fully responsive, afebrile, and hemodynamically stable. His
last recorded transaminases were AST/ALT 43/31 U/L. He was discharged home in stable condition on hospital day 10.Clinical isolates were
obtained from cultures of specimens submitted on the patient. Identification of
bacteria suspected of being streptococci was identified according to standard
bacteriologic criteria. Group A streptococci were initially identified by their
susceptibility to bacitracin and then were grouped in the clinical microbiology
laboratory using StrepPro Streptococcal
Grouping Kit (Hardy Diagnostics, Santa
Maria, Calif, USA). The technique employed was latex agglutination. The patient’sStreptococcus pyogenes was found to be
positive by antibody testing for both streptococcal pyrogenic exotoxin B and C
(SPE B & C); but the SPE A was negative [3].Group A
streptococcus (Streptococcus pyogenes)
is an aerobic gram-positive coccus that causes pharyngitis and a spectrum of
skin and soft tissue infections such as impetigo, erysipelas, and localized
cellulitis [4]. Less commonly, group A streptococci cause invasive
diseases such as bacteremia, necrotizing fasciitis, pneumonia and postpartum
sepsis, and the infection may be complicated by TSS in approximately one-third of patients. The entry points for streptococcal
infections are the pharynx, skin, or vagina. Note, however, that in those
subjects diagnosed with streptococcal TSS,
a point of entry cannot be clearly identified in 45 percent [1].Group A
streptococcal TSS (infection associated with the acute onset of shock and organ
failure), similar to staphylococcal TSS, is mediated by toxins that act as
superantigens, which activate the immune system by circumventing the typical
antigen-mediated immune response pathway. Superantigens
do not require processing by antigen presenting cells but interact directly
with relatively invariant regions of the class II MHC molecules and outside the
groove area [5]. Superantigens
are capable of interacting with an exceedingly large number of T cells. Unlike
a conventional antigen, which evokes a response from less than 0.01% of the
entire T-cell repertoire, a superantigen can interact with 5% to 30% of T cells [6]. This leads
to a release of large quantities of inflammatory cytokines, which results in
leakage of capillaries and tissue damage, subsequently leading to shock and
multiorgan failure [4, 7].It is well known
that streptococcal pyrogenic exotoxins have also been described in group A
streptococci, including types A, B, and C, which are genetically distinct from
each other. These toxins have been shown to be superantigens, and to cause TSS
in animals. In the majority of reported cases of severe group A streptococcal
infection, we have found combinations of SPE A, SPE B, or SPE C to be present,
with SPE A being most common in the US
[2, 8–12]. Reports have
shown that the exotoxin SPE B is largely found in the UK and in Sweden [13, 14],
and there are others characterized such as streptococcal superantigen, which
has been found in M-3 strains [15], and mitogenic factor  (MF), found in
various different M-types [16, 17].Interestingly, most streptococcal
TSS isolates make SPE A or at least contain the gene for SPE A (speA), compared with 15% of non-TSS
isolates [5]. All of the streptococcal-TSS isolates also
carry the SPE B or contain the gene for that toxin (speB); but this is also true of non-TSS strains
[5]. Although recent evidence suggests that
SPE C may also contribute to the illness, the role of SPE B is unclear because
both TSS and non-TSS isolates carry the make this product
[18, 19].  Therefore, it is likely that our strain may not
result in shock; because the SPE A exotoxin is absent.As our patient had a strain
ofS. pyogenes that did produce both
SPE B as well as SPE C which have been shown to be involved with some TSS-like disease, it is possible that our patient
had a MHC II haplotype which was
partially protective. MHCs are highly polymorphic, and given that there are
over 100 different alleles for class I and class II genes in humans, enormous
polymorphism exists [18]. Theoretically, >1012 is the
diversity possible [20]. Susceptibility to a given pathogen or its
toxins may reflect the role of particular MHC alleles in responsiveness or nonresponsiveness to antigens.Of particular
significance is the clinical presentation of this patient relating to the
diagnosis of streptococcal TSS. The presence of rapidly progressive end organ
failure with positive blood cultures often accompanies streptococcal TSS. It has, however, been reported that almost 50
percent of patients with TSS are
found to be normotensive on presentation; however even these patients later
become hypotensive within the subsequent hours
[7, 21]. Interestingly,
our patient was never found to be hypotensive. We therefore have a presentation
of an adult with disseminated group A streptococcal bacteremia with severe
sepsis and nonfocal rhabdomyolysis without associated shock. We believe that our
patient presented with these findings as a result of the absence of SPE A as
well as a possible partial protective effect of the MHC II haplotype. It is
important for clinicians to be aware that Streptococcus
pyogenes can present with toxic shock—like syndromes,
with sepsis and severe organ dysfunction, without evidence of shock.



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*Source: 786451-2009-04-05.xml*