Streptococcal pharyngitis in a Child, Complicated with a Necrotizing Myositis: Diagnosis, Management and Follow-Up

Background

Group A streptococcus (GAS) is a gram-positive aerobic bacterium that is a common cause of pharyngitis in adults and children. In addition, it can also cause severe invasive soft tissue infections, such as cellulitis, fasciitis, and myositis (grouped under the term necrotizing soft tissue infections [NSTI]), bacteremia, and toxic shock syndrome [1–4]. Usually, NSTI at distant sites is not a complication of pharyngitis but rather a distinct clinical entity associated with chronic conditions in adults and trauma, varicella, and surgery in children [1,5]. The presented case is one of the rare occurrences of NSTI and the first described case of GAS myositis developing as a complication of streptococcal pharyngitis and scarlet fever in a child.

Case Report

A 2.5-year-old boy was admitted to the Clinic for Infectious Diseases and Febrile Illnesses of University Medical Center Ljubljana, Slovenia, on behalf of his primary care pediatrician, with diagnoses of scarlet fever and fasciitis of the left shin. Family, prenatal, and perinatal history was normal; the boy underwent normal physical and psychological development, was vaccinated according to schedule, and had not had any contagious diseases to date. With the exception of the transient synovitis of the left hip 1 year before the event, he was otherwise healthy. In the preceding week, his older brother had been ill with a sore throat. The boy fell ill 3 days before being admitted, with a fever up to 41°C and a diffuse erythematous rash over his trunk. Later that day, he started complaining of pain in the left lower leg. The next day he was seen by his primary care pediatrician, who diagnosed scarlet fever and prescribed oral penicillin V 250 mg 3 times per day, not paying particular attention to the pain in the left shin, which the mother had mentioned. The same day his parents noticed that he refused to walk, as well as the presence of edema and redness of the left shin. The fever did not resolve after administration of paracetamol but did lower in response to diclofenac.

At the time of the admission, the boy was calm, had a fever and tachycardia, and the skin of the face was erythematous, sparing the area around the mouth, in the shape of a triangle. Examination of his mouth revealed an unpleasant odor, with a reddened pharynx and enlarged tonsils. He had a typical scarlatiniform eruption on his trunk and lymphadenopathy in the submandibular and inguinal areas, bilaterally. His left shin was grossly edematous, with diffuse bluish discoloration of the skin anterolaterally and pain to palpation (Figure 1). The lower leg arterial pulses were palpable bilaterally. Laboratory investigations revealed markedly elevated inflammatory markers: C-reactive protein level of 476 mg/L (reference <8), sedimentation rate of 76 (reference <15), neutrophilic leukocytosis with left shift and a leucocyte count of 14.7×109 /L (reference 5.1–13.4), with 73% of segmented neutrophils (reference 22–69) and 10% of band forms (normal 0–0.8), and anemia, with hemoglobin of 94 g/L (reference 102–127).

Empiric antibiotic treatment with intravenous (i.v.) benzylpenicillin of 1 million units every 6 h and clindamycin 150 mg every 6 h was immediately initiated after obtaining blood samples for bacterial culture. A diagnostic ultrasound of the left lower leg was performed, revealing pathological changes in the musculature in the lateral and anterior compartment of the left lower shin. Normal morphology of the muscle was absent; the area was heterogenic with smaller areas of fluid with echogenic inclusions. There were no signs of blood flow in the affected muscles, but blood flow in the large vessels between muscle groups was present. There was a small amount of fluid next to the overlying fascia, which indicated possible mild fasciitis. The radiologist diagnosed diffuse necrotizing myositis with marked necrosis of the above-mentioned muscles.

Based on clinical suspicion of NSTI and considering the ultrasound results, the consulting surgeon decided for an urgent operation. An anterolateral fasciotomy of the left shin was conducted, which revealed a 6×3-cm area of necrotic muscles (musculus tibialis anterior and extensor digitorum longus (Figure 2), which was surgically excised (Figure 3). Samples of necrotic muscle and overlying fascia were taken for histological examination, as well as samples for bacterial culture. The open wound was packed with alginate dressing and left open to heal by secondary intention. Postoperatively, the wound was regularly monitored. The dressing change for the first 2 times was done under a short i.v. sedation and analgesia.

The bacterial culture of the intraoperative biopsy revealed Streptococcus pyogenes, sensitive to all tested antibiotics, including penicillin and clindamycin. The bacterial culture of blood samples did not yield results.

Histopathological examination of muscle and fascia taken during surgery revealed severe necrotizing fasciitis and myositis, blood vessel thrombosis, and numerous gram-positive cocci.

On the first postoperative day, markers of muscle necrosis were measured alongside other routine laboratory investigations: creatine kinase level of 9.77 μcat/L (reference <2.85) and myoglobin level of 54.4 μg/L (reference <47.0).

The child continued to receive i.v. benzylpenicillin with clindamycin at initial doses for 10 days postoperatively until the local infection settled. Twelve days after the operation, secondary soft tissue and skin closure was conducted. The patient stayed in the hospital for 4 weeks.

Later on, the boy regularly attended the surgical outpatient clinic for examinations, and the wound healed without complications (Figure 4). At first, he had slight problems with walking because of partial loss of dorsiflexion of the left foot. Six months after the operation, he no longer had problems walking, and dorsiflexion was only slightly worse in comparison to the right foot. At the age of 10 years, he was participating in competitive sports, and the only consequence was a visible scar and slight tissue defect in the left lower leg.

Discussion

Infectious bacterial pharyngitis is a common disease in children and is caused by GAS in more than one-third of cases. In contrast, its incidence is much lower in adults, with 5% to 15% of cases being due to GAS. It presents acutely with sore throat, inflammation of tonsils and pharynx with exudate, palatal petechiae (also known as doughnut lesions), fever, headache, nausea, vomiting and abdominal pain, cervical lymphadenopathy, and possible scarlatiniform rash, whereas in younger children the disease can have an indolent course, with upper respiratory symptoms, low-grade fever, and cervical lymphadenopathy [2,6]. The most common natural progression is spontaneous resolution in up to 5 days; however, there is a small but significant risk of potentially severe complications, such as scarlet fever, rheumatic fever, and glomerulonephritis, as well as local soft tissue infections due to direct spread [2]. Bacteremia secondary to streptococcal pharyngitis occurs in only 0.3% of febrile pediatric patients [3]. Antibiotic therapy is warranted in all symptomatic bacterial pharyngitis cases, confirmed by rapid antigen or culture tests. The standard regimen is oral penicillin V for 10 days, with the dose being 250 mg 2 to 3 times per day for children weighting less than 27 kg and 500 mg 2 to 3 per day for heavier children, and adults. Alternative agents are amoxicillin, clindamycin, and intramuscular penicillin G [7].

Soft tissue necrotizing infections due to group A streptococci, also referred to as type 2 NSTI, encompass a necrotizing form of cellulitis, fasciitis, and myositis, of which fasciitis and myositis are extremely fast progressing, leading to potential high morbidity and mortality [8]. NSTI are rare, with the incidence in adults being 0.04 cases per 1000 person-years and approximately twice as rare in children [5]. Risk factors in adults are smoking, diabetes mellitus, i.v. drug use, and peripheral vascular disease. Risk factors for developing NSTI in children are trauma, surgery, underlying chronic illness such as Down syndrome, congenital neutropenia, cerebral palsy, and varicella infection [5]. The portal of entry is most commonly the skin, due to localized trauma, with the conventional cause being combat wounds or surgery. In other cases, localized skin trauma can be so small as to go unnoticed, such as small skin fissures that grant bacteria access to the lower layers of tissue where they can start spreading, especially in the immunodeficient host, for example, patients with diabetes mellitus. Another type of predisposing injury is widespread but superficial skin damage, such as in varicella or burns [5,9]. Much rarer is presumed hematogenous spread; only a handful of cases of GAS spreading from a primary site to distant sites producing NSTI have been described, with the primary site being the pharynx in most cases [10–14].

For example, in 1992, Boyle and Singer described a case of 12-year-old previously healthy boy presenting with septic shock, acute renal failure, and clinical signs of NSTI on the left thigh. Final diagnosis was necrotizing myofasciitis of the left thigh, and debrided tissue and blood culture was positive for GAS; however, preceding factors and portal of entry were never discovered [12]. Allen described a series of 9 cases in 1994, with patients aged between 11 and 87 years. Five patients had previous blunt extremity trauma, 1 patient was diabetic with abrasion on the foot, 1 patient had a non-characterized upper respiratory tract infection 2 weeks prior, and 1 patient had no probable initiating factor. The report stated the importance of early aggressive surgical treatment, exemplified by the fact that 5 out of 6 patients undergoing surgery early survived, in contrast to 3 patients with a delay in treatment who all died [10]. In 2013, Zink et al described a case of a 45-year-old man with diabetes mellitus type 2 diagnosed with necrotizing myofasciitis following a streptococcal pharyngitis, with blood and debrided tissue cultures positive for GAS and throat swab rapid antigen test positive for GAS [14]. In 2014, Hourmodzi described a case of a 48-year-old woman diagnosed with GAS necrotizing myositis of the iliopsoas muscle. She had recently received a new tattoo on the right back. She had upper respiratory symptoms for the preceding 3 days and claimed that a throat swab was positive for influenza A [11].

Myositis is the rarest form of NSTI, with only approximately 45 cases being described to date, with the addition of 4 cases being discovered in a series of 20 000 autopsies [11]. Interestingly, blunt, non-penetrating trauma is an independent risk factor for developing myositis, which has been explained on a molecular level: healing muscle and/or fascia are more prone to be seeded with streptococci in a setting of (transient) bacteremia. [9] Compared with cellulitis and fasciitis, myositis less frequently causes the skin changes associated with NSTI, namely redness, local warmth, skin induration, petechiae, and bullae; if those features do appear, they are a sign of extensive underlying muscle necrosis. The most diagnostic feature is marked tenderness and edema of the affected area. Another hallmark is elevated laboratory markers of muscle necrosis (creatine kinase and myoglobin), which accompany markedly elevated inflammatory markers. Like fasciitis, myositis is a rapidly progressing infection, which can cause necrosis of whole muscle compartments within hours; it can also lead to compartment syndrome due to extensive swelling inside compartments. Compared with other forms of NSTI, myositis more frequently causes systemic upset and bacteremia. The most severe systemic complication of this infection is streptococcal toxic shock syndrome due to the release of streptococcal exotoxin, which acts as a super-antigen in which the patient progresses to acute distributive shock with organ impairment: renal and liver failure, coagulopathy, and respiratory distress syndrome [4,15].

The patient from the presented case had streptococcal pharyngitis, which was complicated with scarlet fever, a common complication in children. However, the course from the onset was not indolent but rather acute, with high-grade fever from day 1. According to the associated feature of left lower leg pain, which was present from day 1, the streptococci quickly gained access to the blood and subsequently infected the muscle. There was no history of blunt trauma, but this might well have gone unnoticed, especially considering the age of the patient. After an extensive search, the authors believe that the presented case is the first reported occurrence of GAS myositis as a consequence of transient bacteremia following streptococcal pharyngitis in a child.

The clinical course after admission was congruent with the description above: the boy was systemically unwell with tachycardia and fever; however, he did not develop shock during the course of the disease. Pain in the left shin prevented him from walking, and the area was extremely tender. He had some skin changes indicating extensive underlying necrosis, which was later confirmed by ultrasound and surgery. He did not have overt compartment syndrome; pulses were palpable; however, peripheral neurological status was not determined for eventual paralysis or paresthesia. Laboratory muscle necrosis markers were not measured on the day of admission but on the first postoperative day and were still positive; they might have been even higher on the first day. Blood cultures from the samples taken on the day of admission did not yield results, which can be attributable to the fact that the patient received antibiotic therapy from the second day of his illness and was already on antibiotic treatment before blood culture samples were collected.

Because of the quickly progressing nature of NSTI, surgery should be carried out even in the case of suspicion of fasciitis or myositis; the diagnosis is then established by direct observation of necrotic fascia and muscle, which can be excised in the same setting. Imaging studies can be useful to confirm or refute the suspicion of NSTI or to help plan the surgery, but they must not delay surgical exploration. Differentiation between cellulitis, which does not need surgical exploration, and myositis or fasciitis, which do, is difficult; therefore, the diagnosis of myositis or fasciitis should not be prematurely ruled out. The modalities used are ultrasound, computed tomography, and magnetic resonance imaging, with the latter being the most sensitive in detecting fasciitis and myositis [11,15–17]. In the presented case, ultrasound was readily available and did not delay surgical exploration, revealing that myositis rather than fasciitis was prevalent in this case, which helped in planning the surgical intervention. The diagnosis of NSTI, after being established during surgery, can be further confirmed with histopathology, which was the case with the presented patient. Additionally, the frozen sections technique can be used intraoperatively, but the benefits of this are questionable [1].

The basic therapy of necrotizing myositis is bimodal and consists of antibiotic therapy and surgery. The mortality rate with only antibiotic treatment is close to 100% [1]. Surgery consists of a debridement of necrotic tissue until healthy viable tissue is reached. It is important to surgically intervene early and to perform extensive debridement. In certain cases, amputation is the only means of controlling an infection [1,11,18]. Antibiotic therapy for streptococcal NSTI consists of high-dose i.v. benzyl-penicillin (60 000–100 000 units/kg every 6 h) and clindamycin (10–13 mg/kg every 8 h); clindamycin is added because it is, in contrast to penicillin, highly active to non-dividing bacteria (the Eagle effect) and because it blocks bacterial exotoxin production [4,19]. However, empirical therapy of NSTI should target gram-positive, gram-negative, and anaerobic bacteria and methicillin-resistant Staphylococcus aureus, with the proposed antibiotic regimen being piperacillin-tazobactam plus vancomycin, pending culture results [1,19]. Possible adjunctive treatments for NSTI are therapy with hyperbaric oxygen and i.v. immunoglobulin, although their benefit has not yet been proven in high-quality studies [8]. Despite prompt antibiotic treatment in the presented patient, his state deteriorated, demonstrating the need for surgical treatment in the case of NSTI. After surgical exploration, the wound was regularly inspected for any leftover or newly occurring necrotic tissue, but subsequent debridement was not needed. In contrast, patients usually need several sessions of debridement, as reported by Hakkarainen et al [8]. In line with the practice described in the literature, the wound was only closed in the present case when all the local and systemic signs of infection subsided, at which time antibiotic therapy was also stopped [1].

Functional damage from debridement surgery can be extensive, especially in the case of myositis, in which the removal of necrotic muscle is needed. Despite the extensive area of necrosis being described in the preoperative ultrasound, the visually discernible necrotic area and thus tissue loss was smaller in the presented case. Barring the transient loss of function of the lower leg, the patient did not have negative consequences. This contrasts with the high mortality of NSTI reported in most modern studies, which averages between 20% and 40% [8]. The mortality of necrotizing myositis is even higher – according to older reports, it approaches 85% [15]. However, the mortality of necrotizing fasciitis in children is reported to be as low as 5.4% [5]. There are no studies on the mortality of necrotizing myositis in children; however, based on reports on adults, it can be presumed to be higher than in fasciitis. Evidence of the morbidity of NSTI is even more scarce; in 1 study, it was reported that 30% of survivors had mild to severe functional impairment at the time of discharge; however, there was no long-term follow-up [8]. The excellent outcome of the presented case is, therefore, attributable to the young age of the patient, lack of poor prognostic factors, prompt diagnosis, and early and aggressive surgical treatment.

Conclusions

NSTI are rare infections. Furthermore, occurrences of NSTI due to hematogenous spread are even rarer, as opposed to those due to direct spread from the skin. Additionally, NSTI without predisposing chronic conditions such as diabetes mellitus or other types of immunodeficiency are uncommon. However, these infections carry high potential morbidity and mortality, which can be prevented with early and aggressive surgical and antibiotic treatment. Therefore, clinicians must have a low threshold in suspecting NSTI, even when the pathogenesis and presentation is not typical, as in the presented case.