Alabama rot: update on UK cases

The cause remains unknown; optimal strategies for disease prevention and case management are, therefore, yet to be elucidated. The diagnosis can only be confirmed via histopathology of renal tissue, and is, therefore, generally a postmortem diagnosis. The potentially life-threatening nature of CRGV, combined with the large number of unknowns surrounding the disease, have led to a high level of public concern. Vets are, therefore, under increasing pressure to be familiar with the approach to suspected cases.

Over the past six years, cutaneous and renal glomerular vasculopathy (CRGV) has most commonly been recognised between November and May each year, with an apparent peak case incidence in February.

Occasional cases have, however, been presented over the summer and autumn months. To date, June, July and October have had the lowest case number (Figure 1; Anderson Moores Veterinary Specialists, unpublished data). The significance of the possible winter-spring distribution of cases is unknown, but investigations are ongoing.

While CRGV associated with significant acute kidney injury (AKI) appears to be rare – with between 10 and 30 cases reported each year for the past 5 years (Anderson Moores Veterinary Specialists, unpublished data) – the true incidence of CRGV in the UK remains unknown. This is associated with the difficulties of reaching a definitive diagnosis in non-azotaemic cases, along with the voluntary nature of case reporting.

Cases have occurred across much of the UK (Figure 2) and appear to have occurred in small, loose geographical clusters. No evidence exists of the disease being spread directly from dog to dog. Some dogs that have been walked together, even if they do not live together, have become affected concurrently. Given this, and the geographical distribution, an environmental trigger for the disease is suspected, but has yet to be proven or identified.

A lot of speculation has occurred about woodland walking locations being significant in some way, and studies are underway to further investigate the epidemiology of CRGV.

A regularly updated map of confirmed case locations can be found online (Vets4Pets, 2018).

Clinical signs

Erosive or ulcerative skin lesions – preferentially affecting the ventral body, limbs and/or muzzle, and tongue – are the most commonly observed abnormality and, for some cases, skin lesions remain the sole abnormality.

Lesion appearance is variable, ranging from small superficial abrasions, through to large areas of full thickness ulceration and necrosis, with surrounding erythema and oedema (Figures 3 to 8). Lesions may be mistaken for pododermatitis, cellulitis, wounds or bites/stings. Although many dogs are systemically well aside from their skin lesion(s), some will show signs of illness, including anorexia, lethargy, vomiting, diarrhoea, polyuria/polydipsia, pyrexia, increased bleeding tendency (petechiae, epistaxis), neurological signs (seizures, ataxia, behavioural change), lameness and/or icterus (Holm et al, 2015).

Pathogenesis

CRGV is a thrombotic microangiopathy (TMA), characterised by endothelial damage triggering platelet activation, which results in the formation of microthrombi in affected vessels (in CRGV, the small glomerular and dermal arterioles are preferentially affected). The microthrombi gradually narrow and eventually occlude the affected arterioles, reducing blood supply to the organ, which gradually leads to cell death and organ dysfunction. In the kidney this manifests as AKI, while in the skin, necrosis and ulceration result.

During this process, erythrocytes may become damaged as they squeeze through the narrowed arterioles, and are then removed from the circulation by the reticuloendothelial system. The potential result is microvascular haemolytic anaemia. A number of TMAs have been reported in humans (Goodship et al, 2017) and other species, such as rabbits (Garcia et al, 2002), horses (Morris et al, 1987; Dickinson et al, 2008), cattle (Valli and McSherry, 1973; Roby et al, 1987) and cats (Aronson and Gregory, 1999) and, at this time, it is unknown whether the aetiology of CRGV is the same as for any of these conditions.

Approach to suspected cases

Dogs that are systemically well

No single antemortem test exists for confirming a diagnosis of CRGV and, unfortunately, it is not possible to predict which cases will develop AKI. It is, therefore, generally recommended to obtain baseline haematology, biochemistry and urinalysis in a dog with a suspicious skin lesion, even if that dog does not have any signs of systemic illness.

Haematology

The TMA process commonly leads to consumptive thrombocytopenia and possibly microangiopathic haemolytic anaemia. Anecdotally, the development of thrombocytopenia may be one of the earlier changes observed in dogs developing clinically relevant AKI (Anderson Moores Veterinary Specialists, unpublished data).

Some cases have neutrophilia and evidence may exist for microangiopathic haemolysis on smear examination (burr cells, schistocytes; Holm et al, 2015). In cases that do not develop AKI, haematology may be normal at initial presentation and remain normal.

Biochemistry

Some cases are azotaemic at the time of presentation; however, serum urea and creatinine concentrations are insensitive indicators for AKI, and azotaemia may not be documented until relatively late after AKI development.

Changes in urine output or increases in serum creatinine within the reference range may be earlier indicators of AKI.

Other reported possible biochemical abnormalities include increased serum liver enzyme activities, increased muscle enzyme activities and hyperbilirubinaemia (Holm et al, 2015). Serum symmetric dimethylarginine may also be useful to assess as an earlier marker of AKI when compared with serum creatinine concentration (Dahlem et al, 2017).

Again, for cases in which AKI does not develop, serum biochemistry may be normal at the time of presentation and may remain normal during monitoring.

Urinalysis

In cases that remain non-azotaemic, urinalysis may be completely unremarkable. For those that have – or will develop – AKI, urinalysis may reveal similar abnormalities to those seen with AKI of other causes; namely, proteinuria, haemoglobinuria, casts (predominantly granular or hyaline) and glucosuria (Holm et al, 2015).

Urine output can be normal, reduced or increased and should be at least subjectively monitored, as cases can become acutely oligoanuric if AKI develops.

Monitoring

In a systemically well dog – presented solely for assessment of skin lesion(s), without abnormalities on routine haematology, biochemistry and urinalysis – ongoing monitoring and symptomatic management for the skin lesion(s) is likely to be appropriate. Potentially nephrotoxic medications (such as NSAIDs) should be avoided whenever possible.

The frequency of ongoing monitoring should be guided by history, physical examination findings, owner and clinician concern, and considerations such as patient temperament and any financial constraints. Testing can be repeated every 24 hours to 48 hours, or at the owner’s discretion, if no concerns are apparent.

The risk for development of AKI may be greater in dogs with multiple or large skin lesions, with severe surrounding erythema or oedema. However, it is important to note AKI has also developed in dogs with single and/or mild lesions (Holm et al, 2015).

Histopathology

Biopsy of skin lesions of unknown origin can be considered, but the histopathological changes seen in the skin of CRGV cases are often non-specific, including coagulative necrosis and ulceration, with adnexal atrophy. Rarely, vascular fibrinoid necrosis may be observed, which would be supportive of a diagnosis of CRGV (Holm et al, 2015). Skin biopsy may, however, be useful for excluding other causes of these lesions, such as immune-mediated or neoplastic conditions.

Care must be taken with anaesthesia or sedation to avoid lowering mean arterial blood pressure and deleteriously affecting glomerular filtration rate.

Management

Dogs without apparent AKI

As aforementioned, the distinction between dogs likely to remain non-azotaemic, versus those at higher risk for developing clinically relevant AKI, is not clear.

Dogs that have clinical signs other than skin lesions(s) – for example, lethargy, inappetence, pyrexia, vomiting or diarrhoea and/or have laboratory abnormalities, such as anaemia, neutrophilia, thrombocytopenia, hyperbilirubinaemia, haemoglobinuria and/or proteinuria – have significant potential for AKI to develop. Such patients may benefit from admission to hospital for in-patient monitoring and fluid therapy, although it should be noted no evidence exists in people that IV fluid therapy will prevent the development of AKI in euvolaemic patients. Fluid therapy may, however, be required to prevent the patient becoming dehydrated or, rarely, hypovolaemic, if clinical signs such as anorexia, adipsia, vomiting or diarrhoea are present.

Pentoxifylline

Pentoxifylline is licensed in humans for use in the management of peripheral vascular diseases. It has been used in dogs as part of the management for familial dermatomyositis, and for other vasculopathies (Rees and Boothe, 2003).

It may be a beneficial drug to consider in CRGV patients, as it reduces blood viscosity, making erythrocytes more flexible, and also increases fibrinolysis. However, no controlled studies documenting an improved outcome in CRGV patients managed with pentoxifylline exist.

No known benefit associated with the use of steroids at either anti-inflammatory or immunosuppressive doses for dogs with CRGV exists, and their use cannot be recommended.

Prognosis

The prognosis for cases that remain non-azotaemic, or develop only very mild (International Renal Interest Society grade I) AKI, appears to be excellent with appropriate management, although skin lesion healing may have a prolonged time course and some lesions will result in scar formation.

Prevention

Unfortunately, while the aetiology of CRGV remains unknown, no specific guidelines regarding disease prevention exist.

As the highest case incidence is seen over the winter and spring, when walks may be wetter and muddier, it may be sensible to wash dogs after walks, although this recommendation is not evidence-based.

• Anderson Moores Veterinary Specialists is continuing to collate data, and encourages vets with suspected or confirmed cases to contact it by emailing medicine@andersonmoores.com or telephoning 01962 767920.

• Diagnosing and managing AKI caused by CRGV: part 2