Purpura Hemorrhagica Research Articles

Concurrent Streptococcus equi subsp. equi infection, purpura haemorrhagica and immune‐mediated myositis in a Quarter Horse filly

SummaryThis report describes a 2‐year‐old Quarter Horse filly that was diagnosed with concurrent Streptococcus equi subsp. equi infection, purpura haemorrhagica, and immune‐mediated myositis. The filly was presented for evaluation of fever of unknown origin, rapid weight loss and inappetence after exposure to strangles that was initially unknown. Over the course of hospitalisation the filly developed mandibular lymphadenopathy, guttural pouch empyema, and mucosal petechiation and ecchymoses. The presence of Streptococcus equi subsp. equi was confirmed via PCR and culture of a lymph node aspirate and biopsies of the skin confirmed leukocytoclastic vasculitis, consistent with purpura haemorrhagica. Genetic testing confirmed that the filly had one copy of the MYH1 mutation (N/My). Following therapy with systemic corticosteroids, plasma transfusion and antimicrobial therapy the filly improved and was discharged. Communication with the owner 11 months later confirmed that filly appeared healthy but remained poorly muscled. This report is the first to the authors' knowledge describing concurrent Streptococcus equi subsp. equi infection, purpura haemorrhagica, and immune‐mediated myositis.

Spontaneous bilateral superficial digital flexor tendon rupture in a horse with guttural pouch empyema and suspected purpura hemorrhagica

SummaryCase historyAn 11‐year‐old Quarter Horse gelding was evaluated for urticaria, generalised discomfort, distal limb oedema, spontaneous dropped fetlocks, and progressive hindlimb lameness. Prior infection status with Streptococcus equi subspecies equi was unknown.Clinical findingsThe horse had bilateral hindlimb oedema, generalised wheals, progressive hindlimb lameness, and dropped fetlocks of the right and left hindlimbs. The horse was intermittently pyrexic and was ultimately subjected to euthanasia due to deteriorating clinical status.DiagnosisSuspected purpura hemorrhagica associated with leukocytoclastic vasculitis of the superficial digital flexor tendons and spontaneous tendon rupture.Treatment and outcomeThe horse was treated with a combination of antibiotic therapy (enrofloxacin and penicillin), nonsteroidal anti‐inflammatory drugs (phenylbutazone) and corticosteroids (dexamethasone), with no improvement in clinical status. The horse was subjected to euthanasia due to poor prognosis and unfavourable response to therapy. Post‐mortem examination revealed unilateral guttural pouch empyema, multifocal cutaneous infarction and bilateral rupture of the superficial digital flexor tendons. Streptococcus equi subspecies equi was isolated in pure culture from the guttural pouch. Microscopically, leukocytoclastic vasculitis typical of purpura hemorrhagica was documented in the skin. Unexpectedly, similar vasculitis was also observed in the superficial digital flexor tendons.Clinical relevanceThis report documents the first equine case of suspected purpura hemorrhagica associated with leukocytoclastic vasculitis of the superficial digital flexor tendons and spontaneous tendon rupture. Spontaneous tendon rupture should be considered a potential sequela to infection with Streptococcus equi subspecies equi in horses due to immune‐mediated vasculitis.

Fabry disease: a short history of the eponym

Fabry disease (Anderson-Fabry disease) is a rare genetic lysosomal disorder that affects the heart, kidneys, and the central nervous system (CNS). The disease is caused by mutations in the GLA gene, located in the X chromosome. The disorder was first described by both Johannes Fabry, dermatologist, and William Anderson, surgeon, independently in 1898. Johannes Fabry (1860–1930) was born in Jülich, Germany. He studied medicine in Bern and Berlin, where he received his doctorate in 1886. Between 1889 and 1929, Fabry served as chief medical officer of the Skin Clinic at Dortmund. In 1898, he described dermatological features of the disease in a 13-year-old boy and named the condition „purpura haemorrhagica nodularis“. In the same year, William Anderson (1842–1900) reported the disorder in a patient aged 39 years. He described eruptions on his trunk and on the right leg. Anderson termed the condition „angiokeratoma“. The patient’s mother and sister as well three of his four children were also affected by the disease. Anderson was born in London. He was educated in Lambeth School of Art, and in St. Thomas Hospital. In 1873, he moved to Tokyo, Japan, where he served as professor of anatomy and surgery.

Strangles, convalescent Streptococcus equi subspecies equi M antibody titers, and presence of complications.

Background Streptococcus equi subspecies equi infection elicits M protein antibody titers in equids. Interpretation of titers is not generally accepted.HypothesisThe magnitude of S. equi M protein (SeM) antibody titer after infection (titer ≥1:12 800) will be useful to monitor for the presence of complications or the risk of development of complications.AnimalsForty‐eight horses on 1 farm involved in strangles outbreak.MethodsClinical and observational study. S. equi M protein antibody titers were measured on all horses 8 weeks after infection and select horses 12 and 28 weeks after infection. Horses were categorized: no disease, uncomplicated case, persistent guttural pouch (GP) infection, or complicated cases (metastatic abscesses, purpura hemorrhagica, secondary infections, and dysphagia). Category was compared to titer.ResultsTwenty‐eight of 48 (58%) developed clinical signs of S. equi infection. Of those, 11 (39%) had uncomplicated strangles, 9 (21%) had persistent GP infection, 5 (18%) were complicated cases, and 3 (11%) had both persistent GP infection and complications. Thirty‐three percent of horses (16 of 48) had SeM antibody titers ≥1:12 800 eight weeks after infection. Of horses with titers ≥1:12 800, 6 of 16 had evidence of complications. Of complicated cases, 6 of 8 had titers ≥1:12 800. In this outbreak, the sensitivity (75%; 95% CI [confidence interval] 45‐105) for a SeM antibody titer ≥1:12 800 detecting complications was higher than the specificity (43%; 95% CI 23‐64).Conclusions and Clinical ImportanceThis outbreak demonstrates that SeM antibody titers can be increased after infection (≥1:12 800) in the absence of complications of strangles.

Staphyloccocus aureus‐associated infarctive purpura haemorrhagica, immune‐mediated haemolytic anaemia and myocarditis in a Quarter Horse mare

SummaryA 7‐year‐old Quarter Horse mare was presented for severe left hindlimb oedema and nonweightbearing lameness that was progressive over approximately 48 h. The mare subsequently developed marked and worsening oedema, immune‐mediated haemolytic anaemia (IMHA), myositis and myocarditis. The marked oedema, degree of pain and severity of myositis were consistent with infarctive purpura haemorrhagica. Fine needle aspiration of affected tissue resulted in positive bacterial culture of Staphylococcus aureus. Purpura haemorrhagica and associated complications are typically associated with Streptococcal sp. infection or exposure, and have not been previously reported in association with Staphylococcus aureus in the horse. The mare responded favourably to long‐term, high‐dose corticosteroid therapy, antimicrobials and supportive care.

Immune-Mediated Muscle Diseases of the Horse.

In horses, immune-mediated muscle disorders can arise from an overzealous immune response to concurrent infections or potentially from an inherent immune response to host muscle antigens. Streptococcus equi ss. equi infection or vaccination can result in infarctive purpura hemorrhagica (IPH) in which vascular deposition of IgA-streptococcal M protein complexes produces ischemia and complete focal infarction of skeletal muscle and internal organs. In Quarter Horse-related breeds with immune-mediated myositis, an apparent abnormal immune response to muscle antigens results in upregulation of major histocompatibility complex class (MHC) I and II on muscle cell membranes, lymphocytic infiltration of lumbar and gluteal myofibers, and subsequent gross muscle atrophy. Rarely, an inflammatory event results in myositis with subsequent systemic calcinosis characterized by a pathognomonic hyperphosphatemia and high fatality rate. This review presents an overview of these immune-mediated myopathies and highlights clinical and pathological features as well as the suspected pathophysiology.

Strangles and its complications

SummaryStrangles, caused by the Gram‐positive bacteriaStreptococcus equisubspeciesequi(S. equi), is a highly contagious upper respiratory infection in horses. The infection is transmitted by inhalation or direct contact with mucopurulent discharge from an infected animal, resulting in fever, depression, and submandibular and retropharyngeal lymph node enlargement that can lead to respiratory distress. Complications include secondary cellulitis at external abscessation sites, guttural pouch empyema and its persistence into the carrier state, purpura haemorrhagica, metastatic abscessation, emergency tracheostomies and rarely secondaryS. equipneumonia or myositis. Control of outbreaks requires strict isolation protocols and hygiene measures. Detection methods of the index case and carrier state are constantly being refined to assist in the identification and prevention of disease perpetuation.

Presumptive purpura haemorrhagica and deep digital flexor tendonitis associated with S. equi subsp. equi infection in a Thoroughbred foal

Presumptive purpura haemorrhagica and deep digital flexor tendonitis associated with S. equi subsp. equi infection in a Thoroughbred foal

Predictor variables for and complications associated with Streptococcus equi subsp equi infection in horses.

To evaluate predictor variables for and complications associated with Streptococcus equi subsp equi infection (strangles) in horses. Retrospective case-control study. 108 horses with strangles (cases) and 215 horses without strangles (controls). Medical records from January 2005 through July 2012 were reviewed. Cases were defined as horses with clinical signs of strangles (pyrexia, retropharyngeal lymphadenopathy, and mucopurulent nasal discharge) that were associated with a confirmed strangles outbreak or had positive results for S equi on PCR assay or bacteriologic culture. Controls were defined as horses with pyrexia that did not meet the other criteria for cases. Data compared between cases and controls included signalment, clinical signs, diagnostic test results, and disease complications and outcome. Logistic regression was used to identify variables associated with strangles and its complications. Clinical signs of strangles were not evident in 12 of 25 cases classified as S equi carriers (infected > 40 days). Predictor variables associated with strangles included mucopurulent nasal discharge and external abscesses in the pharyngeal region. Strangles was more likely to be diagnosed in the spring than in the summer. Cases with anemia were more likely to develop purpura hemorrhagica than were cases without anemia. No risk factors were identified for the development of guttural pouch empyema or metastatic abscesses. Results indicated that not all horses infected with S equi develop clinical signs of strangles. We recommend that guttural pouch endoscopy and lavage with PCR assay of lavage fluid samples be performed to identify S equi carrier horses.

Lessons learned from a strangles outbreak on a large Standardbred farm

SummaryStreptococcus equisubspecies (ssp.)equiinfection (strangles) remains one of the most frequently diagnosed and costly infectious diseases of horses. Large breeding herds, where a disease outbreak competes for personnel and financial resources needed for foaling management, present a special challenge for equine practitioners. A 15‐month outbreak involving 62 clinical cases of strangles occurred on a large Standardbred breeding farm (average population of 1400 horses). Sixteen asymptomatic horses were found to be PCR (polymerase chain reaction)‐positive forS. equissp.equi. During the outbreak, serological samples from 48 clinically normal horses were found to be seropositive forS. equissp.equi, confirming herd‐wide exposure. After several clinical cases of strangles had been diagnosed, an intranasalS. equissp.equivaccine was administered to clinically normal horses (n = 558) considered to be at risk of exposure. Strangles complications included 7 fatalities (none in vaccinated horses) and 6 cases of purpura haemorrhagica (4 in vaccinated horses). Midway through the outbreak, injectable, sustained release ceftiofur crystalline free acid (CCFA), given as an initial dose followed by a second dose 4 days later, was used exclusively for systemic antimicrobial treatment of clinically affected and PCR‐positive horses. This antimicrobial regimen coincided with a reduction in disease incidence and eventual resolution of the outbreak. Two horses with persistent guttural pouch infection were endoscopically confirmed as carrier horses. The herd history demonstrated that a strangles outbreak will often result in asymptomatic carrier horses and that identification and treatment of these horses are necessary to eliminate long‐term sources of infection. Ceftiofur crystalline free acid was found to be a suitable antimicrobial due to its activity againstS. equissp.equiand the efficiencies associated with twice parenteral dosing during a 10‐day treatment period. Occurrence of purpura in 4 vaccinated horses suggests that vaccination should be reserved for healthy seronegative horses and avoided during an active outbreak.

Cerebellar peduncle abscess secondary to disseminated strangles in a six-week-old miniature foal

During a strangles outbreak within a herd of minature horses, a six week old foal developed acute onset clinical signs of sepsis and neurological deficits. The foal was euthanized and submitted for post-mortem at the Animal Health Laboratories, Guelph Ontario. Gross <em>post-mortem</em> examination noted severe bronchopneumonia, hypopyon of the right eye and a singular cerebellar peduncle abscess. Culture of the lungs and cerebellum produced a pure growth of <em>Streptococcus equi</em> ssp. <em>equi</em>. <em>Streptococcus equi</em> ssp. <em>equi</em>, the causative agent of equine strangles, produces an acute pyrexia, purulent lymphadenopathy of submandibular and retropharyngeal lymph nodes. Commonly, lymph node abscesses rupture and resolve without complication. Rarely, complications may include: dissemination of the bacteria with diffuse abscess formation, immune mediated disease (purpura haemorrhagica), rarely abscess formation within the central nervous system (CNS) can occur. These can be managed medically with appropriate antibiotics and drugs to reduce intra-cranial pressure, however surgical drainage and debulking of the abscess has been attempted successfully in a few cases.

Sequelae and complications ofStreptococcus equisubspeciesequiinfections in the horse

SummaryStreptococcus equissp.equiinfection in the horse, or strangles, commonly results in abscessation of the submandibular, submaxillary or retropharyngeal lymph nodes. Although this classical presentation of strangles is associated with a low mortality rate, complications and sequlae may worsen the prognosis and increase mortality rates. This article reviews sequelae and complictions ofS. equissp.equiinfection in the horse, including guttural pouch empyema, bastard strangles and immune mediated diseases such as purpura haemorrhagica, myopathies and myocarditis.

PARACLINICAL ASPECTS OF HEMOSTASIS DISTURBS IN PURPURA HEMORRHAGICA OF THE HORSES

A number of 20 work horses, clinically healthy (group no.1, control group) and 9 work horses with purpura hemorrhagica (group no.2) were investigated paraclinically using the parameters of the minimum balance of homeostasis. In both groups we determined the prothrombine time (PT), partial activated thromboplastine time (APTT) and fibrinogen. Using the average value of PT in group no.1 and group no.2 we calculated the INR value (International Normalized Ratio). The values of PT, APTT and INR were increased in horses from the 2nd group (PT= 56,43 ±86,48s; APTT = 95,53 ±14,81s; INR = 5,03) compared to the average values of the same parameters in the horses from group no. 1 (PT = 11,19 ±1,76s; APTT = 58,17 ±11,72s; INR = 1,10). Plasmatic fibrinogen was of 183 ±49,46 mg/dl in the horses of the 1st group and 136 ±57,57 mg/dl in the horses of the 2nd group.

Could we eradicate strangles in equids?

Views: Commentary 377 S (Streptococcus equi subsp equi infection) is a globally distributed and highly contagious equine scourge first described by veterinarians of ancient Rome. Outbreaks are associated with loss of condition, disruption of training and riding activities, cost of veterinary care, and lethal sequelae including disseminated (bastard) strangles and purpura hemorrhagica. The overall complication rate can be as high as 20% of affected animals, with a case fatality rate of up to 8%. Control of strangles is based on various approaches, including screening, quarantine, and immunization. Fully effective and safe vaccines providing long duration of immunity are not available, and the task of developing such vaccines, even with complete genome sequence data for S equi and Streptococcus zooepidemicus, is recognized to be considerable. A recent American College of Veterinary Internal Medicine consensus statement from the United States and United Kingdom on guidelines for treatment, control, and prevention was 12 pages, a length that emphasizes the complexity of control measures. In the United Kingdom, the Codes of Practice Guidelines on Strangles published by the Horserace Betting Levy Board is shorter and, like the consensus statement, focused on dealing with outbreaks. It notes the advisability of informing the relevant breeders’ associations of infection, but acknowledges that there is no legal requirement for this, even for purposes of export. There are no guidelines in Canada agreed to by the horse industry. Strangles has all the hallmarks of an infection that should and could be eradicated (Appendix 1). The causative agent replicates only in equids and survives only briefly in the environment. It causes serious loss through morbidity and death, as well as through cost and implementation of control measures in outbreaks. Because it is not reportable, its presence may fail to be disclosed for economic or other reasons, and therefore, the disease may be introduced unknowingly causing demoralization and conflict. Recent work has shown that the organism is a unique biovar or genovar of an ancestral S zooepidemicus. It appears to be genetically frozen, and unlike most pyogenic streptococcal species, antigenic variation of surface virulence-associated proteins including SeM is slight or absent. In many ways, S equi is an archaeologic relic that could be consigned to history. Could we eradicate strangles in equids?

Streptococcus equi subsp. equi (Strangles) Infection

Streptococcus equi subsp. equi infection (strangles) is an acute, contagious upper respiratory tract disease of predominantly young horses characterized by rhinopharyngitis and lymphadenitis of the submandibular and retropharyngeal lymph nodes. S. equi infects the host by attaching to tonsillar epithelium after inhalation or ingestion of infected secretions. Several components of the bacterium, including the capsular M-protein, contribute to virulence and immunogenicity. Nasopharyngeal mucosal and systemic immune responses are important for recovery, and most naturally infected horses become solidly immune for years thereafter. Definitive diagnosis is made by culture or polymerase chain reaction testing of nasal swabs, abscess aspirates, or guttural pouch lavages. Treatment is dependent on the stage and severity of disease. Inapparent carrier horses play an important role in persistence of S. equi and its transmission to susceptible populations. Control and prevention depend on isolation of affected horses, appropriate sanitation, identification of carriers, and judicious use of vaccines. Complications from S. equi infection include guttural pouch empyema, internal abscesses, purpura hemorrhagica, and myositis.

The research of immunologic function change by using sipulin and prednisone to treat 48 cases of idiopathic purpura haemorrhagica

目的 观察斯普林与泼尼松对特发性血小板减少性紫癜的细胞免疫功能的改变.方法随机分为两组,斯普林与泼尼松为治疗组48例,单用泼尼松对照组45例,采用流式细胞仪分别测定两组患者用药前后T细胞亚群及NK细胞活性的变化.结果治疗组治疗后患者CD8阳性百分率明显低于对照组、CD4+/CD8+值显著高于对照组(P＜0.05),NK细胞活性百分率略高于对照组(P＞0.05).结论斯普林可有效地改善特发性血小板减少性紫癜的免疫功能。

Cutaneous Markers of Disorders Affecting Adult Horses

In adult horses, skin lesions and changes in the haircoat may serve as primary owner complaints for underlying systemic diseases. Cutaneous markers of systemic disorders of adult horses may include crusting or nodular dermatopathies (eg, photosensitization consequent to liver disease, purpura hemorrhagica, idiopathic granulomatous disease, multisystemic eosinophilic epitheliotropic disease, or lymphoma) or haircoat changes (eg, alopecia or hirsutism) that should alert equine practitioners and dermatologists alike to search for underlying primary disease processes. Diseases with skin manifestations range from those in which the skin is one of the primary organs affected (eg, idiopathic granulomatous disease or multisystemic eosinophilic epitheliotropic disease) to those for which dermatological lesions are secondary and resolve with treatment of the underlying disease (eg, photosensitization consequent to liver disease). This review focuses on disorders for which skin lesions or haircoat changes are markers for systemic diseases in adult horses.

Cutaneous Markers of Disorders Affecting Young Horses

In adult horses, skin lesions and changes in the haircoat may serve as primary owner complaints for underlying systemic diseases. Cutaneous markers of systemic disorders of adult horses may include crusting or nodular dermatopathies (eg, photosensitization consequent to liver disease, purpura hemorrhagica, idiopathic granulomatous disease, multisystemic eosinophilic epitheliotropic disease, or lymphoma) or haircoat changes (eg, alopecia or hirsutism) that should alert equine practitioners and dermatologists alike to search for underlying primary disease processes. Diseases with skin manifestations range from those in which the skin is one of the primary organs affected (eg, idiopathic granulomatous disease or multisystemic eosinophilic epitheliotropic disease) to those for which dermatological lesions are secondary and resolve with treatment of the underlying disease (eg, photosensitization consequent to liver disease). This review focuses on disorders for which skin lesions or haircoat changes are markers for systemic diseases in adult horses.

Infarctive purpura hemorrhagica in five horses

Five horses were examined because of signs of muscle stiffness, colic, or both. All 5 had been exposed to Streptococcus equi within 3 weeks prior to examination or had high serum titers of antibodies against the M protein of S equi. Horses had signs of unrelenting colic-like pain and focal areas of muscle swelling. Four horses were euthanatized. The fifth responded to treatment with penicillin and dexamethasone; after 3 weeks of treatment with dexamethasone, prednisolone was administered for an additional 10 weeks. Common hematologic and serum biochemical abnormalities included neutrophilia with a left shift and toxic changes, hyperproteinemia, hypoalbuminemia, and high serum creatine kinase and aspartate transferase activities. Necropsy revealed extensive infarction of the skeletal musculature, skin, gastrointestinal tract, pancreas, and lungs. Histologic lesions included leukocytoclastic vasculitis in numerous tissues and acute coagulative necrosis resembling infarction. These horses appeared to have a severe form of purpura hemorrhagica resembling Henoch-Schönlein purpura in humans and characterized by infarction of skeletal muscles. Early recognition of focal muscle swelling, abdominal discomfort, neutrophilia, hypoalbuminemia, and high serum creatine kinase activity combined with antimicrobial and corticosteroid treatment may enhance the likelihood of a successful outcome.

Purpura haemorrhagica in 53 horses

The medical records of 53 horses with purpura haemorrhagica were reviewed. Seventeen of them had been exposed to or infected with Streptococcus equi, nine had been infected with Corynebacterium pseudotuberculosis,...