Group G Streptococcal Toxic Shock-Like Syndrome in Three Cats
Three 8-week-old kittens were presented with a history of acute, generalized weakness and severe fever. One cat was dead upon presentation, and necropsy findings were supportive of a group G Streptococcus spp. septicemia. During their clinical courses, two of the three kittens developed a progressive, marked swelling of one or more limbs. One moribund and severely hypothermic cat was euthanized a few hours after presentation, and necropsy was also supportive of a group G Streptococcus spp. septicemia. One kitten recovered. Group G streptococcal toxic shock-like syndrome was suspected because of the fulminant progression of the septicemia.
Case Reports
History
Three 8-week-old, Oriental shorhair littermates were presented to the referring veterinarian with 2- to 7-day histories of generalized weakness and dysorexia. Upon physical examination, oral ulcers and pyrexia (104° to 107.6°F) were noted in all three cats. Marked swelling of distal joints was also found. Serological evaluations for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) using enzyme-linked immunosorbent assay (ELISA) were negative for all three kittens. The kittens were given enrofloxacina (5 mg/kg intramuscularly [IM] q 24 hours) and ketoprofenb (1 mg/kg subcutaneously [SC] q 24 hours) for a suspected bacterial infection and management of the pyrexia. Within 48 hours, the cats were anorexic, and the swelling of the distal joints had progressed to generalized swelling of one or more limbs in two of the three cats. The remaining cat was found dead and was submitted for necropsy. The two live kittens were referred to the University of Montreal Small Animal Veterinary Teaching Hospital for evaluation and supportive care.
The affected kittens were born in an open cattery from a multiparous queen and had two other littermates. One sibling was asymptomatic, and the other had recently received an injection of lincomycinc (22 mg/kg IM) for lethargy and had recovered uneventfully. All the kittens received their first vaccination (feline panleukopenia virus, feline herpesvirus, feline calicivirus, and Chlamydia psittaci) 10 days prior to presentation.
When the kittens were 6 weeks old, the queen developed a severe mastitis and was treated with a 5-day course of amoxicillin/clavulanic acidd (62.5 mg per os [PO] q 12 hours). The mastitis worsened, requiring partial mastectomy. The amoxicillin/clavulanic acidd was continued for 14 days, and the queen completely recovered. Because of the queen’s surgery, the kittens were weaned and placed with an adoptive queen. The adoptive queen was healthy, and her last litter occurred 6 months earlier. Vaccination status of the queens was current.
Case No. 1
The 0.85-kg male kitten was lethargic and 7% dehydrated upon presentation. Temperature, pulse, and respiratory rate were 100.5°F, 240 beats per minute, and 70 breaths per minute, respectively. The kitten was not dyspneic. The pulses were strong and regular. Mucous membranes were pale, but capillary refill time (CRT) was normal. Oral ulcers were present at the margins of the tongue. Cardiac auscultation and abdominal palpation were unremarkable. Inspiratory and expiratory pulmonary sounds were increased bilaterally. Right hind-limb lameness, secondary to marked swelling of the entire limb, was noted. The limb had pitting edema and was warm, but not painful. The right popliteal lymph node was not palpated because of the marked swelling, but the left inguinal lymph node was markedly enlarged, firm, and painful. Neurological examination was normal except for a proprioceptive defect, an absent withdrawal, and an absent patellar reflex in the right hind limb. Upon presentation, the rectal temperature was normal, but ketoprofenb had been given in the previous 12 hours.
Diagnostic evaluation included a complete blood count (CBC) and a serum biochemical profile. Laboratory findings included a nonregenerative (absolute reticulocyte count, 15,880 × 106/L), normocytic, normochromic anemia (hematocrit [Hct], 17%; reference range, 28% to 34%) and a neutrophilia (21.4 7times; 103 cells/μL; reference range, 5.75 to 12.4 times; 103 cells/μL) with a left shift (band neutrophils, 1.7 times; 103 cells/μL; reference range, 0 to 0.3 times; 103 cells/μL). The presence of Doehle bodies, cytoplasmic basophilia, and foaminess suggested a toxic leukogram. Serum biochemical profile abnormalities included a mildly elevated glucose (192.7 mg/dL; reference range, 69.0 to 143.6 mg/dL) and a low-normal albumin (2.34 g/dL; reference range, 2.3 to 3.00 g/dL). Thoracic survey radiographs showed a severe, diffuse, interstitial pulmonary pattern. Pneumonia associated with a viremia or a septicemia was suspected, but noncardiogenic edema of the lungs could not be excluded.
Treatment consisted of lactated Ringer’s solution (10 mL/kg per hour for 2 hours, supplemented with 16 mEq/L of potassium chloride and 25 mL of 50% dextrose) to provide cardiovascular support. The heart rate and the respiratory rate decreased to 200 beats per minute and 50 breaths per minute, respectively, and the kitten became more responsive. The fluids were gradually tapered as the general condition of the kitten improved. Ampicilline (30 mg/kg intravenously [IV] q 8 hours) was administered, and once hydration was corrected, amikacinf (20 mg/kg IV q 24 hours) was given to broaden the antibacterial spectrum of the antibiotics.
Cytology of a fine-needle aspirate of the left inguinal lymph node revealed a suppurative septic inflammation. A group G Streptococcus spp. (i.e., gram-positive, cocci, beta-hemolytic, catalase-negative, Lancefield group G) in pure culture was isolated from the left inguinal lymph node. Antibiotic testing confirmed the isolate was sensitive to ampicillin, and amikacin administration was stopped. The left inguinal lymph node abscessed on day 3, and the wound eventually healed by second intention. Cytopathology of a fine-needle aspirate of the right hind-limb swelling had low cellularity and revealed a mildly proteinaceous fluid compatible with edema. Hydrotherapy and physiotherapy of the right hind limb were initiated once cavitary lesions were ruled out based on ultrasonography of the limb.
On day 7, the IV fluids were stopped because the cat was eating normally, and amoxicilling (30 mg/kg PO q 12 hours) was started. By day 9, the edema of the right hind limb had resolved, but a severe lameness persisted. The conscious proprioception reflex and the patellar reflex were still absent, but the withdrawal reflex was normal. Thoracic radiographs showed a partial resolution of the interstitial pattern. The kitten was bright, alert, eating normally, and was discharged on day 9 on oral amoxicillin.
On day 18, thoracic radiographs revealed resolution of the interstitial pulmonary pattern. Amoxicillin was continued for another 7 days. The lameness persisted, reflexes in the limb were unchanged, and the range of motion of the right stifle was significantly reduced. On day 40, the cat weighed 1.3 kg, and his gait was markedly improved. The patellar reflex was present but was decreased, as was conscious proprioception. One year later, the cat weighed 3.6 kg, had a normal gait, and had normal neurological function of the right hind limb.
Case No. 2
The 0.90-kg female kitten was moribund upon presentation. She was 7% dehydrated and had a temperature, pulse, and respiratory rate of 99°F, 150 beats per minute, and 60 breaths per minute, respectively. The pulses were weak but regular. Mucous membranes were pale, and CRT could not be evaluated. Cardiac auscultation and abdominal palpation were unremarkable. Inspiratory and expiratory pulmonary sounds were increased. Oral ulcers were noticed at the margins of the tongue. The entire right thoracic limb and the right stifle had pitting edema, were warm to the touch, but not painful. Peripheral lymphadenopathy was not observed. The neurological examination was difficult to perform and assess because of severe depression.
A CBC revealed a nonregenerative (absolute reticulocyte count, 25,600 times; 106/L), normocytic, normochromic anemia (Hct, 11%); a lymphopenia (1.2 times; 103 cells/μL; reference range, 8 to 11 times; 103 cells/μL); a neutropenia (3.8 times; 103 cells/μL) with a left shift (band neutrophils, 1.3 times; 103 cells/μL); and a severe toxic leukogram (presence of Doehle bodies, cytoplasmic basophilia, and foaminess). The serum was mildly icteric. A sufficient amount of blood could not be retrieved in order to confirm the hyperbilirubinemia. The total solids were decreased (4.4 g/dL; reference range, 5.5 to 8.0 g/dL). Thoracic radiographs revealed a diffuse interstitial pattern, and some air bronchograms were noticed in the mid-portion of the left lung. Based on the radiographs, a bacterial pneumonia was considered likely, although noncardiogenic edema and concurrent aspiration pneumonia could not be excluded.
Treatment consisted of lactated Ringer’s solution (10 mL/kg per hour for 2 hours, supplemented with 16 mEq/L of potassium chloride and 25 mL of 50% dextrose) to provide vascular support, and ampicilline (30 mg/kg IV q 8 hours). Within hours, the left thoracic limb and the left hind limb became severely edematous, the cat became severely hypothermic (95°F) despite warming efforts, and the owner elected euthanasia.
A necropsy was performed. Severe subcutaneous edema and mild, pleural, pericardial, and abdominal effusions were found on gross pathology. A fibrinous exudate with moderate infiltration of macrophages was observed in the skin. Numerous septic emboli (i.e., gram-positive cocci) were visible in the pulmonary arterial vasculature. Edema was occasionally seen within the alveoli, and septal inflammation was observed. Edema, necrosis, and hemorrhage were documented in the myocardium. The bone marrow was extremely cellular, and all cell lines were present. Marked necrosis adjacent to the centrolobular vein of the liver with occasional thrombosis was observed. A group G Streptococcus spp. was cultured from the liver, the kidney, and the spleen. A culture of the lung yielded no growth. Necropsy findings were compatible with thrombosis and vasculitis with secondary necrosis (mainly in the myocardium and the lungs, and to a lesser extent in the liver, the kidneys, and the skin) from a group G streptococcal septicemia. The central nervous system was not evaluated.
Case No. 3
The dead, 0.83-kg female kitten was submitted for necropsy. Gross necropsy revealed subcutaneous edema of the ventral aspect of the thoracic wall and mild pleural effusion with a severe multifocal pleuritis. On histopathology, numerous colonies of gram-positive cocci, along with a fibrinous exudate, were seen at the surface of the pleura and in the adjacent pulmonary parenchyma. The parenchyma also demonstrated moderate inflammation (i.e., degenerate neutrophils). The right cranial lobe and the accessory lobe were firm and atelectatic. Numerous septic emboli (i.e., gram-positive cocci) were visible in the pulmonary arterial vasculature. Edema and macrophages were sometimes seen within alveoli. The pericardium was severely edematous, and a fibrinous exudate with colonies of gram-positive cocci were also seen. Mixed inflammatory foci were observed in the epicardium. Microthrombi were seen in the hepatic sinusoids, and bacterial emboli were observed in a centrolobular vein. A group G Streptococcus spp. was isolated from the lungs, the liver, and the thoracic fluid. Considering the histopathological results and the bacterial culture, a group G Streptococcus spp. septicemia was suspected.
Discussion
In 1978, a multisystemic syndrome was recognized in humans that progresses rapidly to sepsis and secondary complications; it was attributed to a toxin-producing Staphylococcus aureus bacterium.1 In 1983, it was reported that Streptococcus pyogenes (Lancefield group A) may produce toxins that share similar biological properties with the toxin of S. aureus.2 Streptococcus pyogenes was then suspected to be responsible for a toxic shock-like syndrome and the development of a necrotizing fasciitis in humans.2–4 It was hypothesized that the toxin acts as a superantigen and triggers T cells to respond by releasing different inflammatory cytokines.5 Detection of antibody directed against toxins produced by S. pyogenes has been reported.6 In 1995, a similar syndrome with or without necrotizing fasciitis in mature dogs was identified, and Streptococcus canis (Lancefield group G) was involved.7–10 In 1996, White reported a necrotizing skin and subcutaneous streptococcal (Group g) infection in four, otherwise healthy cats.11
Streptococcus canis is part of the normal bacterial flora of both cats and humans.12 The acquisition of virulent factors by the bacteria may explain the newly recognized manifestations of this organism.13 It is suspected that the production of a toxin is involved in the syndrome reported in dogs and cats, but the exact toxin that may act as a super-antigen has not yet been identified.1314 Recently, Ingrey et al. suggested that a S. canis bacteriophage, which may cause mild spontaneous lysis of the bacterium, may favor the development of the streptococcal toxic shock syndrome in the presence of enrofloxacin.14 Enrofloxacin may cause a marked bacteriophage-induced lysis of S. canis that results in the liberation of superantigen responsible for the streptococcal toxic shock syndrome.14 Further studies are needed to confirm this hypothesis.
The signs associated with the streptococcal toxic shock syndrome in dogs are depression, pyrexia, and the development of rapidly progressive hypotension leading to multiple organ failure.79 Respiratory signs from pulmonary involvement have also been reported.79 Necrotizing fasciitis, a gas-forming, fulminate, necrotic infection of the superficial and deep fascia, resulting in thrombosis of the subcutaneous blood vessels, has sometimes been associated with streptococcal toxic shock syndrome.9 Intense pain is a consistent finding when necrotizing fasciitis is observed, and a history of minor trauma 12 to 48 hours prior to presentation has been reported.9
Depression, pyrexia, and respiratory signs were predominant findings in all three cats reported here. Because of the small size of the kittens, indirect blood pressure could not be measured, but findings such as depression, tachycardia, dehydration (in case nos. 1, 2), and weak pulses (in case no. 2) strongly suggested a hypotensive state. Septic emboli, thrombosis, hemorrhage, and necrosis seen in the lungs, the myocardium, and the liver of case nos. 2 and 3, and in the kidneys and the skin of case no. 2, suggested multiple organ failure. Although swelling of the limbs was noted, cytological (case no. 1) and histopathological (case no. 2) findings were not compatible with necrotizing fasciitis.
Because the clinical presentation and clinical course of these kittens were compatible with prior reports in cats, and a group G Streptococcus spp. was isolated in all three kittens, a diagnosis of a group G streptococcal toxic shock-like syndrome was made. The fact that case no. 1 survived the disease indicated that, as with S. pyogenes in humans, individuals infected with the same bacteria can develop very different clinical manifestations.5 Biochemical tests to characterize the group G Streptococcus spp. isolated are not routinely performed by the authors’ laboratory, because S. canis is the agent from the Lancefield group G that is most commonly isolated in domestic animals, as opposed to Streptococcus dysgalactiae subspp. equisimilis in humans.34
The diffuse subcutaneous edema and the pleural, peritoneal, and pericardial effusions found at necropsy in case no. 2, and to a lesser extent in case no. 3, may have resulted from increased vascular permeability secondary to inflammatory mediators, because vasculitis was not a predominant feature. Upon presentation, none of the cats had received fluids, but the right hind limb of case no. 1 and the right thoracic limb and right stifle of case no. 2 were already severely edematous. These findings supported the conclusion that crystalloid administration (20 mL total), even though total solids were low in case no. 2, was not the sole explanation for the diffuse edema seen on the postmortem examination. A systemic inflammatory response syndrome (SIRS), possibly resulting from septicemia, was thought to be responsible for the increased vascular permeability. The alveolar edema seen at necropsy (case no. 2) and the swelling of the right hind limb (case no. 1) may also have been a manifestation of SIRS.
The diffuse, interstitial pulmonary pattern (case nos. 1, 2) on thoracic radiographs was compatible with pneumonia from bacterial or viral origin, although noncardiogenic edema could not be ruled out. A bronchoalveolar lavage was not performed in either case because of the small size of the animal and the high anesthetic risk. The histopathological findings in case no. 2 showed some inflammation in the septum of the alveoli, bacterial emboli of the arterial vasculature, and alveolar edema compatible with noncardiogenic edema, possibly from SIRS. Despite the presence of bacteria on histopathology, the lung culture yielded no growth. In case no. 3, the atelectatic right cranial and accessory lobe, the presence of inflammation in the pulmonary parenchyma, and a group G Streptococcus spp. positive lung culture supported a diagnosis of bronchopneumonia. The multifocal pleuritis most likely resulted from an extension of the bronchopneumonia and the septic emboli to the pleural cavity.
The anemia in case nos. 1 and 2 maybe occurred from inadequate erythropoiesis, as kittens may have a delayed response to anemia.15 Blood loss and vasculitis could not be excluded. Increased red blood cell (RBC) fragility secondary to toxemia was another possible contributing factor to the anemia, although suspicious alterations in RBC morphology was not observed on hematology. Peripheral RBC destruction could not be excluded as a cause for the anemia in case no. 2. The hypercellularity of the bone marrow in case no. 2 was not surprising given the age of the animal, although it contrasted with the anemia, the neutropenia, and the left shift seen on the blood count. This hypercellularity suggested an acute condition. Inflammatory mediators, such as interleukin (IL) − 1, can stimulate neutrophil differentiation and proliferation in the bone marrow, which leads to myeloid hyperplasia.16 The maturation process usually takes up to 4 days before segmented neutrophils are released.17 The neutropenia and left shift probably resulted from the massive peripheral demand, whereas the toxic leukogram resulted from the bacterial nature of the underlying process. Lymphopenia may have been caused by stress or a viral infection. The neutrophilia seen in case no. 1 may have indicated a less fulminant form of the disease, one in which the bone marrow was able to overcome the peripheral demand. Coagulation profiles and blood cultures would have been helpful in both cases, but they were not performed because of the small size of the kittens.
In case no. 1, the neurological deficits in the right hind limb were compatible with lower motor neuron damage to the femoral and sciatic nerves. These deficits were assumed to be from the severe edema, which may have resulted in ischemic and mechanical damage, thus altering nerve conduction. As the sciatic nerve deficit had resolved by day 9, neuropraxia, a transient interruption of nerve function and conduction sometimes associated with lesions involving the myelin, was suspected. The neurological examination on day 40 revealed improved function of the right femoral nerve. Given the clinical improvement, axonotmesis of the right femoral nerve was suspected. Axonotmesis is defined as a nerve injury in which a detachment of the axon from the neuronal cell body occurs. As the endoneurium and the Schwann sheath remain intact, regeneration of the axon is possible at a rate of approximately 1 inch per month. The fact that the kitten had a prolonged but complete neurological recovery supported a diagnosis of axonotmesis. Septic emboli of the gray matter of the spinal cord were also considered possible causes of the neurological deficits, but they were less likely because of the severity of the initial clinical signs and the complete recovery.
Streptococcus canis septicemia is common in neonatal kittens, but in juvenile cats the clinical manifestations of infection (i.e., cervical lymphadenitis, arthritis) are not usually severe.18–20 Factors such as malnutrition, poor environmental conditions, concurrent viral infection, and immunosuppression may be predisposing factors in the development of septicemia in older kittens.1021
Signs of upper respiratory disease were not present, but oral ulcers, anorexia, pyrexia, and joint swelling were noted 2 to 7 days after all three kittens received their initial vaccines. These signs, especially the joint involvement, may have represented a viral infection, such as calicivirus. A transient immunosuppression related to vaccine administration may also have contributed to the development of the septicemia. The peracute course of case nos. 2 and 3 and the possible presence of a SIRS made a group G Streptococcus spp. septicemia and streptococcal toxic shock-like syndrome likely.
The bacterial cultures and sensitivity test results were identical in all three kittens, supporting the hypothesis that all the kittens were infected by the same source. The queen’s mastitis may have been the source of infection, although the length of time from inoculation to development of clinical signs was quite long. Unfortunately, the bacteriological agent involved in the mastitis was never identified.
Conclusion
Based upon clinical and necropsy findings, Group G streptococcal toxic shock-like syndrome was suspected in three Oriental shorthair littermates. As these are the first documented cases of this syndrome in cats, it is important for clinicians caring for such cases to document the clinical course and gather important historical information on each case. This information will be critical in identifying predisposing factors to infection and further characterizing clinicopathological data associated with S. canis.
Enrofloxacin; Bayer, Inc., Toronto, Ontario, Canada
Ketoprofen; Merial Canada, Baie D’Urfé, Quebec, Canada
Lincomycin; Pharmacia Animal Health, Orangeville, Ontario, Canada
Amoxicillin/clavulanic acid; Pfizer Canada, Inc., London, Ontario, Canada
Ampicillin; Ayerst Veterinary Laboratories, Guelph, Ontario, Canada
Amikacin; Ayerst Veterinary Laboratories, Guelph, Ontario, Canada
Amoxicillin; Pfizer Canada, Inc., London, Ontario, Canada
