Group A Beta-Hemolytic Streptococcal Glossal Necrotizing Myositis – Case Report and Review

Abstract and Introduction

Abstract

We report the first case of glossal necrotizing myositis by group A beta-hemolytic Streptococcus in an 8-year-old girl on chronic nonsteroidal anti-inflammatory drugs, immunomodulators, and steroids for juvenile rheumatoid arthritis. Treatment included partial glossectomy and parenteral antibiotics. After a critical course, full recovery ensued. The subject of necrotizing myositis is reviewed.

Introduction

Necrotizing myositis (NM) is a precipitous and potentially life-threatening infection, primarily characterized by muscle necrosis, noninvolvement of adjacent fascia, and lacking abscess formation. Invasive group A beta-hemolytic Streptococcus (GABHS) NM is rare in children and has not been previously reported to involve facial structures. There is controversy surrounding the potential role that immunomodulators and nonsteroidal anti-inflammatory drugs (NSAIDs) play in the development of this entity. We report the first case of a rapidly developing GABHS NM involving the tongue in a child being treated with rofecoxib, infliximab, and steroids for juvenile rheumatoid arthritis. A streptococcal toxic syndrome complicated the patient's clinical course.

Case Presentation

At presentation, AD was an 8-year-old child with a history of juvenile rheumatoid arthritis controlled by oral prednisolone (1 mg every other day), infliximab (200 mg monthly), and rofecoxib (25 mg daily). According to AD's mother, during the evening prior to presentation, her daughter developed what appeared to be a “canker sore” on her tongue and a fever to 101°F. By phone consult, the child's covering pediatrician prescribed benzocaine gel (Anbesol) and mouthwash. Progressively worse facial swelling developed throughout the night. By morning, the child had developed significant facial edema and a markedly swollen, purple-black tongue protruding from her mouth.

On presentation, the child was noted to be very anxious, scared, and unable to verbalize, with moderately labored nasal respirations. Vital signs revealed her to be afebrile with a respiratory rate of 22, heart rate of 170 bpm, room-air O₂ saturation of 93%, and weight of 21.0 kg. Physical examination was notable for marked facial swelling of the cheeks, lips, and chin areas. There was no wheezing or stridor appreciated. Her tongue was ecchymotic, swollen, and protruding from between the lips with scant dried blood around the mouth. The nose, ears, and eye exams were normal. The neck was full with midline tracheal position and no crepitus. Chest and abdominal exams were normal. The child was moving her extremities well, but given her tenuous airway, she was gently calmed to prevent overexertion.

AD was administered ceftriaxone, decadron, diphenhydramine, and epinephrine after establishing intravenous access. Oxygen supplementation was provided by face mask. Pediatric surgery, otolaryngology, and intensive care services were consulted and the child was taken emergently to the operating room for nasotracheal intubation. CT scanning showed soft-tissue swelling of the tongue and neck structures without accompanying free air. Laboratory studies were normal except for an elevated white blood cell count of 20.9 × 10⁹/L (72% band forms, 25% granulocytes, 1% lymphocytes, 2% monocytes) and lactate of 3.8 mmol/L. Tissue biopsies confirmed the diagnosis of NM of the tongue with massive bacterial infiltration and vascular thrombosis.

Over the course of the first 24 hours, AD's condition rapidly worsened. She developed septic shock complicated by a coagulopathy. A fine erythematous rash was noted over her lower extremities and trunk. A norepinephrine infusion was required for hypotension. Clindamycin and piperacillin-tazobactam were used as initial broad-spectrum antibiotic coverage. Preliminary biopsy cultures grew GABHS. The next day, AD was transferred to the regional pediatric referral center for surgical evaluation. There she was placed on aztreonam, vancomycin, clindamycin, and acyclovir antimicrobial coverage pending final organism confirmation, along with norepinephrine for hemodynamic instability. A partial glossectomy was performed with removal of the entire front tip back to the attachment of the frenulum. GABHS as the sole pathogen was isolated, sensitive to both clindamycin and penicillin G. During the postoperative period, AD's clinical course was complicated by acute respiratory distress syndrome and a worsening of her rash. The latter was subsequently attributed to a piperacillin-tazobactam allergy.

Over the next several weeks, AD improved slowly. She eventually completed a 3-week course of clindamycin antibiotic coverage. At 2 years, AD continues to do well with enough residual tongue tissue to allow for normal swallowing function and adequate speech ability with the presence of only a very mild speech impediment.

Discussion

First named as a unique disease entity by Nather in 1985,[1] fewer than 25 cases of NM have appeared in the English literature, with this being the first case of glossal involvement (Table). NM is characterized by histologic evidence of myositis, vascular thrombosis, and necrosis of muscle tissue without suppuration. By contrast, necrotizing fasciitis, or “Streptococcal gangrene” when etiologically GABHS, involves superficial tissue necrosis with tracking along fascial planes and sparing of underlying muscle. A similar entity, suppurative glossitis, is an inflammation of the tongue associated with pus formation and typically involves Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus hemolyticus, Trichomonas species, or Capnocytophagia microorganisms.[2–5] Additionally, a noninfectious tongue necrosis has been described as a consequence of giant cell as well as systemic vasculitis, with the latter having been reported as a delayed complication of a streptococcal infection.[6]

Table.

Summary of Reported Cases of Necrotizing Myositis^*

Author	Year	Age/Sex†	Meds‡	Site§	Abx¶	Surg‖	Death	Micro£
Barrett	1958	33/M	Z	lLE	pcn	Y	Y	GABHS
Svane	1971	32/M	U	Glu	pcn	Y	Y	GABHS
		30/M	U	Pec	none	N	Y	GABHS
Chambers	1974	18/M	Z	rLE	cph, stp	Y	N	PS, BS
Mac Laurin	1977	49/F	U	UE	pcn	Y	Y	GABHS
Aitken	1982	69/F	U	LE	U	U	Y	Stp
		40/F	U	UE	U	U	Y	Stp
		49/M	U	LE	U	Y	N	Stp
		39/M	U	LE	U	Y	N	Stp
		81/M	U	LE	U	Y	Y	Stp
Adams	1985	53/M	Z	lLE	pcn, mth, gen	Y	Y	GABHS
		40/F	Z	lLE	pcn, chl	Y	Y	GABHS
Nather	1985	11/M	Z	Hip	pcn	Y	N	GABHS
		22/F	Z	Abd	pcn	Y	N	Stp
Jansen	1988	39/M	Z	lLE	amp, gen, mtr	Y	N	GABHS
Doebbeling	1989	76/M	S	rUE	pcn, gen, van	Y	N	GABHS
Schattner	1989	70/F	Z	rLE	cez, gen	N	Y	GABHS
Boyle	1992	12/M	N	rLE	amp, cef, naf	Y	N	GABHS
James	1992	60/F	Z	Thx	U	N	Y	GABHS, SA
Hird	1994	17/M	N	rLE	pcn	Y	N	GABHS
Marck	1996	36/M	S	lUE	pcn, flu, gen	Y	N	GABHS
Wagner	1996	64/F	N	rLE	brd	N	Y	GGS
Kang	1998	33/M	N	rLE	U	Y	N	Stp
Tang	2001	5/F	Z	Hip	amx/cla, cli	Y	N	GABHS
Baevsky	2005	8/F	NCIS	T	cli	Y	N	GABHS

^*Summary of the English MEDLINE cases of necrotizing myositis, defined as infectious muscle necrosis with noninvolvement of adjacent fascia and lacking any abscess formation.

^†Age (yrs); M = male, F = female

^‡Immunosuppressant medication use at time of diagnosis: S = Steroids; N = NSAID; C = COX-2 inhibitor; U = unknown use; I = immunomodulator (infliximab); Z = none

^§Site of infection: Abd = abdomen; Glu = buttocks; Hip = hip; LE = lower extremity; Pec = pectoralis; T = tongue; Thx = thorax; UE = upper extremity; r = right; l = left

^¶Antibiotic administered: U = unknown; amp = ampicillin; amx = amoxicillin; brd = broad spectrum (unspecified); cef = cefuroxime; cez = cephazolin; chl = chloramphenicol; cla = clavulanate; cli = clindamycin; cph = cephalothin; flu = flucloxacillin; gen = gentamicin; mth = methicillin; mtr = metronidazole; naf = nafcillin; pcn = penicillin; stp = streptomycin; van = vancomycin

^‖Surgical intervention: Y = yes; N = no; U = data unavailable

^£Microbial organism(s): BS = Bacteroides subtilis; GABHS = Group A beta-hemolytic streptococcus; GGS = Group G streptococcus; PS = Peptostreptococcus; SA = Staphylococcus aureus; Stp = Streptococcus (not otherwise specified)

Most reported cases of NM are caused by GABHS, a facultative anaerobe that, although a normal colonizer of the skin and mucous membranes, is an infrequent cause of infection to deep tissue structures. Both local and systemic complications of GABHS infections are most often due to the M1 and M3 subtypes, with the specific subtype not determined in this case report. GABHS production of proteases such as hyaluronidase, streptolysin, and proteinase contribute to local invasive processes. GABHS is also capable of causing a pyrogenic exotoxin-mediated streptococcal toxic shock syndrome, presumably via release of histamine and activation of the complement and kinin pathways. Similar to a staph toxic shock syndrome, a resulting systemic shock state including acute renal failure and the acute respiratory distress syndrome may develop.

In the case presented, AD had a highly refractory case of juvenile rheumatoid arthritis that was being treated with an atypical medication regimen. Although NSAIDs were previously believed to predispose a patient to invasive GABHS infections by inducing a mild immunosuppression or masking signs and symptoms of disease progression, they are not currently considered a risk factor.[7] The COX-2 inhibitors are not as well studied, and a direct causal relationship between the NSAID rofecoxib and the development of NM is circumspect at best. Infliximab, a chimeric monoclonal antibody that acts by binding tumor necrosis factor, ultimately decreases C-reactive protein levels and inflammatory arthritic damage caused by JRA. Infliximab has been associated with an increased risk of infections, more commonly respiratory and opportunistic, with a small subset of patients developing pancytopenia.[8] Steroids are well known to induce immunosuppression. Although benzocaine is a well-documented cause of methemoglobinemia and, rarely, contact dermatitis, neither of these 2 entities appeared to play a contributing role in the case presented.

In diagnosing NM, a high index of suspicion must be maintained for those patients who are immunocompromised or have diminished tissue vascularity, as they are at increased risk. In the case presented, although the tongue has a rich vascular network, it has a minimal arterial supply that potentially predisposes the tissue to ischemic injury and poor response to therapy. GABHS NM can result from direct traumatic inoculation (a bitten tongue may have served as a potential source in the case presented) or from a distant hematogenous seeding.[9] On clinical examination, the appearance of the overlying skin may vary, ranging from normal to resembling necrotizing fasciitis with signs of necrosis and violaceous bullae. Muscle strength may be decreased, with active and passive movement eliciting pain. Radiographic plain films and computed tomography scans may aid in the diagnosis by demonstrating intramuscular gas. Laboratory testing may reveal a leukocytosis with a left shift, a normocytic normochromic anemia, and an elevated erythrocyte sedimentation rate. Metabolic acidosis may develop with or without the presence of extensive necrosis. Hypocalcemia is associated with extensive tissue necrosis and poorer outcomes.[10] Gram staining, cultures, and biopsies of infected tissues are necessary for determination of the organism(s) involved and definitive diagnosis.

Treatment for GABHS NM must be implemented immediately. Basic stabilization with attention to airway, breathing and circulation (ABCs) should be rapidly accomplished. In this case, because of the extensive tongue involvement, nasotracheal intubation was initially attempted. If unsuccessful, a surgical airway would have been secured. When appropriate, patients should be admitted to an ICU setting for close hemodynamic and respiratory monitoring. Compartment pressures should be measured if signs and symptoms of an extremity compartment syndrome are noted. Initially, broad-spectrum empiric antibiotic coverage is warranted until definitive identification of the causative organism can be determined. Once GABHS is identified, intravenous penicillin and clindamycin therapy should be initiated. GABHS is considered universally sensitive to either antibiotic, but despite a 5% resistance in the United States to clindamycin, this antibiotic yields a lower mortality in a controlled mouse model and in uncontrolled retrospective human studies.[11] This outcome is likely secondary to clindamycin's efficacy unaltered by the Eagle effect.Administration of intravenous immunoglobulin may also improve outcome; however, controlled studies are lacking to support its efficacy. Surgical debridement, when added to IV antibiotics, is associated with reduced mortality from 100% to 37% in patients with NM (Table).

Hyperbaric oxygen (HBO) treatment increases partial oxygen tension in infected tissues, thereby inhibiting growth of anaerobic bacteria. Although there is literature describing efficacy of HBO treatment in the management of other invasive GABHS infections, little data exist regarding application of HBO to GABHS NM specifically. Additionally, use of maggot therapy has been described for head and neck soft-tissue debridement when surgery is anatomically prohibited.[12]

In summary, GABHS NM is a rare, rapidly progressive infection with potentially serious systemic sequelae. A high level of clinical suspicion must be maintained in those patients at increased risk. Involvement of the neck and face is rare, with this being the initial case report of specific involvement of the tongue. Treatment should be focused on emergent surgical debridement in conjunction with the use of appropriate IV antibiotics and supportive care.