History
A 6-year-old 500-kg (1,100-lb) sexually intact female warmblood was evaluated because of severe, rapidly developing subcutaneous edema involving all 4 limbs, the ventral aspect of the abdomen, and the head.
Clinical and Gross Findings
On physical examination, the horse was unwilling to move and extremely lame, especially in the hind limbs. The skin of the distal portions of the limbs had multifocal, ulcerative lesions with leakage of a clear fluid (serum) and sloughing, findings that were consistent with dermal necrosis. Petechial and ecchymotic hemorrhages were obvious in all visible mucous membranes, including those of the mouth and vagina. Dyspnea and dysphagia had developed as a result of swelling around the nasal and oral cavities and larynx. The horse was hyperthermic and tachycardic. Ultrasonography revealed splenomegaly with protrusion across the midline to the right side. The horse had neutrophilia; blood biochemical analysis revealed high creatine kinase activity (460 U/L; reference interval, < 395 U/L) and high blood lactate concentration (2.3 mmol/L; reference interval, < 1.0 mmol/L).
Treatment of the horse included administration of broad-spectrum antimicrobials, an analgesic agent, a glucocorticoid, and parenteral nutritional support (dextrose and electrolyte-containing fluids) and other supportive interventions. Two days later, the horse's condition deteriorated rapidly, and it developed severe signs of colic despite administration of flunixin meglumine and butorphanol tartrate. The horse was euthanized by means of an IV overdose of pentobarbital under anesthesia upon the owner's request because of its poor prognosis.
Postmortem examination revealed a sharply delineated, 27 × 25-cm area of reddish to black discoloration at the cecal base (Figure 1). The remainder of the cecal wall was severely thickened (up to 2.7 cm in thickness; reference interval,1 < 0.45 cm). A blood vessel adjacent to the affected area had similar reddish to black discoloration. There were severe, acute, multifocal, petechial hemorrhages on the oral and vaginal mucosae, parietal and visceral pleurae, lungs, myocardium, and pericardium as well as in the mediastinum. Widespread hemorrhages and edema were present in the subcutaneous tissue of all limbs and the ventral aspect of the abdomen, in the caudal thigh muscles, and subperitoneally in the middle to caudodorsal aspects of the abdomen. The right retropharyngeal lymph node was slightly enlarged, and approximately 2 mL of pus drained from its cut surface.
Photograph of the cecum (A) and lungs (B) of a 6-year-old warmblood that was evaluated because of severe, rapidly developing subcutaneous edema involving all 4 limbs, the ventral aspect of the abdomen, and the head. At the base of the cecum, there is a 27 × 25-cm sharply demarcated area of reddish to black discoloration. A blood vessel (arrows) supplying the altered area of the cecum also has reddish to black discoloration. The lungs have severe, acute, multifocal petechial hemorrhages. Similar lesions were found in the oral and vaginal mucosae, parietal and visceral pleurae, heart, and mediastinum. Hemorrhages were present subperitoneally in the middle to caudal dorsal aspects of the abdomen and were widespread in the subcutis and skeletal muscle. In panel A, bar = 5 cm; in panel B, bar = 10 cm.
Citation: Journal of the American Veterinary Medical Association 255, 2; 10.2460/javma.255.2.173
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic and Microbiological Findings
Tissue samples were processed for histologic examination and stained with H&E stain in adherence with standard protocols. For microbiological examination, a swab sample was collected from the right retropharyngeal lymph node. For detection of aerobic bacteria, the swab sample was plated on Columbia blood agar (5% sheep blood), Gassner agar, and chromogenic medium for the presumptive diagnosis of urinary tract–related organisms and incubated for 24 to 48 hours at 36°C. For evaluation of the presence of obligate anaerobic bacteria, the swab sample was plated on Columbia blood agar with l-cysteine, hemin, vitamin K1, and 0.5% lysed sheep blood with and without gentamicin and incubated anaerobically for 48 to 72 hours at 36°C. Chocolate agar was used for cultivation of fastidious bacteria, and inoculated plates were incubated in 7% CO2 for 24 to 48 hours at 36°C.
To semiquantitatively assess the amount of bacterial growth, an unquantitated amount of pus from the swab was applied to the agar and diluted by streaking out bacteria from the inoculation site with a sterile bacteriologic loop. The amount of growth on the agar was then reported semiquantitatively as low (1 to 29 colonies), moderate (30 to 100 colonies), or high (> 100 colonies). Species identification was performed by colony morphology evaluation, Gram staining, and catalase testing in accordance with standard protocols as well as by matrix-assisted laser desorption-ionization time-of-flight mass spectroscopy.
Histologic examination of sections of cecal tissue revealed that all layers of the cecal wall, but predominantly the submucosa, were severely thickened by marked edema and acute hemorrhages. Multifocally, coagulative necrosis was present in all layers of the cecal wall; however, the outer layers were most severely affected (consistent with cecal infarction). In areas adjacent to the necrotic foci, vessels were disrupted; their walls were expanded by deposition of fibrin admixed with few, mainly degenerate neutrophils and necrotic debris (leukocytoclastic vasculitis). Endothelial cells were swollen (reactive hypertrophy) or partially desquamated. There was perivascular infiltration of leukocytes, most of which were degenerated neutrophils with few macrophages. Despite prior treatment with a high dosage of a glucocorticoid, similar vascular lesions were found in nearly all other organs examined but were particularly severe in the subcutis (Figures 2 and 3), skeletal and cardiac musculature, and lungs as well as the other portions of the gastrointestinal tract. Findings of histologic examination of the right retropharyngeal lymph node confirmed abscess-forming lymphadenitis.
Photomicrograph of a section of the subcutis of the ventral aspect of the abdomen from the horse in Figure 1. The subcutaneous blood vessel in this image has evidence of leukocytoclastic vasculitis. The vascular wall and perivascular tissue are extensively infiltrated by mostly degenerated neutrophils, fewer macrophages, necrotic debris, and deposits of fibrin. There is marked perivascular edema. H&E stain; bar = 100 μm. Inset—Higher-magnification view of the same tissue section. Notice the moderately hypertrophied endothelial cells and perivascular infiltration by mostly degenerate neutrophils. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 255, 2; 10.2460/javma.255.2.173
Photomicrograph of another subcutaneous blood vessel with leukocytoclastic vasculitis in the subcutis of a limb from the horse in Figure 1. The vascular wall is largely obscured by severe infiltration of mostly degenerated neutrophils, few macrophages, necrotic debris, and deposits of fibrin that extend into the perivascular tissue. Endothelial cells are severely hypertrophied or partially desquamated. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 255, 2; 10.2460/javma.255.2.173
The microbiological culture of a right retropharyngeal lymph node swab sample yielded low numbers of Streptococcus equi ssp equi despite the horse's previous treatment with 2 antimicrobial agents. It should be acknowledged that taking samples for culture after administration of antimicrobial agents often interferes with microbial growth.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: generalized severe, acute, diffuse leukocytoclastic vasculitis with petechiae, edema, and necrosis; focal infarction of the cecum; and mild, chronic, focal, abscess-forming lymphadenitis of the right retropharyngeal lymph node.
Case summary: S equi–associated purpura hemorrhagica–induced generalized vasculitis associated with intestinal thrombosis and consecutive focal intestinal infarction in a horse.
Comments
Purpura hemorrhagica, a syndrome formerly known as morbus maculosus equorum, is characterized by a generalized leukocytoclastic vasculitis.2 The most striking histopathologic feature of this aseptic, immune-mediated vasculitis is the degeneration and karyorrhexis of neutrophils. Although not fully understood, the pathogenesis of purpura hemorrhagica involves a typical type III hypersensitivity reaction, which is associated with antigen-antibody complex deposition in blood vessel walls and consequent production of activated complement components. The activated complement components drive the recruitment, activation, and ultimately the degranulation of peripheral blood granulocytes with subsequent generalized vascular damage and increased vascular permeability. The resultant characteristic clinical signs include petechial to ecchymotic mucosal hemorrhages and subcutaneous edema that predominantly affect the limbs, the ventral aspect of the abdomen, and the head,2 as was evident in the case described in the present report.
The most common cause of purpura hemorrhagica is a previous infection with gram-positive S equi ssp equi; this type of infection is also known as strangles. Other possible causes include bacterial or viral infections with Rhodococcus equi and Corynebacterium pseudotuberculosis or equine influenza virus and herpesviruses, respectively.3,4 In the case described in the present report, results of the microbiological culture of the lymph node sample strongly suggested an infection with S equi ssp equi as the cause of purpura hemorrhagica. Strangles is one of the most common equine bacterial infections worldwide, and it usually affects the upper respiratory tract of horses. Typically, the disease is characterized by mucopurulent nasal discharge and abscess formation in various lymph nodes, especially those of the rostral region of the neck and head. However, subclinical or clinically mild forms of the disease may also develop. Purpura hemorrhagica develops in approximately 5.4% to 6.5% of horses with strangles, and clinical signs become evident approximately 2 to 4 weeks after infection.5,6 Vaccination of horses with a product containing S equi M-protein provides questionable protection and may provoke development of purpura hemorrhagica.3
In horses with purpura hemorrhagica, the primary aims of treatment are to suppress the immune response with long-term administration of corticosteroids and to remove the antigen stimulus by systemic antibiosis. Penicillin has been considered the antimicrobial of choice for diseases associated with S equi spp equi.2 For the horse of the present report, an alternative regimen of antibiosis was chosen because of the horse's high risk of aspiration pneumonia caused by dysphagia. In addition, supportive care may include application of counter-pressure limb bandages, hydrotherapy, and IV fluid therapy.2,4 Thrombophlebitis at catheter sites is a common complication that may require anticoagulative treatment as occurred in the case described in the present report.4,7 The diagnosis of a leukocytoclastic vasculitis can be confirmed by histologic examination of full-thickness skin biopsy specimens; these specimens should be collected prior to administration of immunosuppressive drugs because such treatment may considerably reduce histopathologic evidence of vasculitis.3 Diagnosis of S equi–associated purpura hemorrhagica can be further supported by results of bacterial cultures and serologic assessments (ie, detection of very high serum concentrations of S equi M-protein–specific antibodies).2
In a study by Pusterla et al,3 the overall survival rate among 53 horses with purpura hemorrhagica was 92.5%. However, the prognosis for horses with purpura hemorrhagica is generally difficult to determine because of the reported variation in clinical disease and complication rates > 20%.6 Complications include dermal necrosis with leakage of serum and sloughing, laryngeal edema, thrombophlebitis, glomerulonephritis, and colic.4,8,9 Specific causes of purpura hemorrhagica–related colic include severe edema, hemorrhages, and necrosis of the pyloric region wall or small or large intestinal walls with potential consecutive gastric rupture, intestinal intussusception or torsion, or rectal prolapse.9–12 If secondary intestinal complications develop, the prognosis is often considered poor, and euthanasia may be indicated.9,11 Infarctions as a result of vascular damage are most commonly located in the skeletal musculature and less frequently in the lungs and skin.3,11 However, to our knowledge, infarction has been very rarely reported to be located in the intestinal tract.10,11 The case described in the present report involved a horse with purpura hemorrhagica–related cecal infarction, with colic as the most striking clinical sign and cause of the rapid deterioration of the horse's condition.
References
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11. Kaese HJ, Valberg SJ, Hayden DW, et al. Infarctive purpura hemorrhagica in five horses. J Am Vet Med Assoc 2005;226:1893–1898.
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