Cutaneous and renal glomerular vasculopathy (CRGV) is a rare, potentially life-threating, disease of unknown aetiology often characterised by ulceration of the distal extremities in dogs. It is sometimes referred to as Alabama rot because some of the initially reported cases in the 1980s were associated with a dog racing park in Alabama, USA. All U.S. cases were reported in greyhounds. It was hypothesised the disease could have been caused by enterotoxigenic E. coli due to the practice of feeding a raw beef diet, but this association was not confirmed.

Since 2012, CRGV has been recognised in more than 280 dogs of various breeds in the UK, but the highest risk groups are those classified as hounds, gundogs, and pastoral dogs such as Labradors, spaniels and Hungarian vizslas. There have now been cases in 47 of the 48 counties in the UK, with over 91% of the cases occurring between November and May. Affected dogs in the UK can be male or female and of any age. Dogs have generally been walked in woodland areas. Affected dogs will generally present with skin lesions on the distal limbs, particularly the digits and pads. The tongue and ventrum are also commonly affected. There is no single reliable ante-mortem diagnostic test available. A presumptive diagnosis is generally made based on clinical history, signalment, and findings, with confirmation being achieved by histopathological identification of thrombotic microangiopathy (TMA) in renal or skin biopsies. CRGV is a TMA wherein endothelial damage leads to platelet activation and microthrombi formation. CRGV is variably associated with clinically significant renal azotaemia, secondary to acute kidney injury (AKI); some dogs develop skin lesions without AKI (i.e. non-azotemic CRGV). The median time from skin lesion identification to AKI recognition is 3 days, with the majority of cases (98%) having shown evidence of AKI within 13 days of development of skin lesions. Remarkably, times of up to 45 days have been reported from skin lesion identification to recognition of AKI. The median IRIS AKI grade at time of recognition is III. Fewer than 2% of cases will present with AKI before skin lesions have been identified. Common clinicopathological abnormalities include thrombocytopenia (84%), neutrophilia (54%), pre/non-regenerative anaemia (29%), hyperbilirubinaemia (52%) and increased liver enzyme activity (e.g. increased ALT activity in 77% of dogs). Abnormalities on urinalysis include proteinuria (92%) and glucosuria (29%). Of relevance, is the fact these findings may develop at different times throughout the disease process. The prognosis for azotemic CRGV patients is guarded. Dogs with presumed or confirmed non-azotemic CRGV would be expected to have a good outlook. As the aetiology currently remains unknown, appropriate management of AKI, lesion management and analgesia are the mainstays of treatment; no specific therapy has been shown to improve outcome. Treatment goals for the patient with AKI are aimed at limiting further renal damage and enhancing cellular recovery. Correction of fluid, electrolyte and acid-base disorders, achieving and maintaining normotension and establishing/maintaining urine flow are the most important aspects of therapy in patients presenting with AKI. Oligoanuria has been reported to develop during the disease process in 43% of cases of CRGV. Furosemide is used as first-line therapy to reverse oligoanuria, followed by mannitol. Dialysis (peritoneal dialysis or continuous renal replacement therapy [CRRT]) may be required in cases refractory to medical therapy. These techniques may be limited by their availability (including facilities and trained staff) and associated financial implications. Therapeutic plasma exchange (TPE) has also been reported as a potential therapeutic option. CRRT and TPE are considered for select cases, but their benefit remains uncertain.

TMAs in humans include but are not limited to haemolytic uraemic syndrome (HUS), complement-mediated HUS, and thrombotic thrombocytopenic purpura (TTP). HUS is primarily caused by Shiga toxin-producing E. coli, and it typically manifests as microangiopathic haemolysis and AKI. Complement-mediated HUS is typically caused by genetic abnormalities leading to the upregulation of the complement system. It generally manifests as AKI and haemolysis and, in some patients, ulcerative skin lesions affecting the extremities also develop. A potential trigger for disease development is suspected, as not all individuals identified with the genetic abnormalities develop disease, and it often occurs in adulthood. TPE is often used in the acute setting, and eculizumab, a C5 complement inhibitor, is the treatment of choice thereafter. Eculizumab therapy has greatly improved outcome, from a condition with high mortality to one wherein successful management is an accepted norm. TTP is generally an immune-mediated condition, where autoantibodies develop against ADAMTS13, an enzyme which regulates thrombosis. Clinical signs are most commonly neurological due to the TMA process being most severe in the capillaries of the CNS. TTP appears the least clinically similar condition to what we see in dogs with CRGV. TPE is typically the treatment of choice, to remove autoantibodies, with rituximab, an anti-CD20 antibody, used in refractory cases.

Further studies are required to better understand the potential benefit of CRRT and TPE in dogs with CRGV. No studies have provided support for the use of eculizumab in dogs with CRGV and the associated expense may be prohibitive in veterinary medicine. Current areas of CRGV research include the complement system, faecal microbiome and circulating endothelial cells. Familial relationships between affected dogs and epidemiological factors are also being studied. Ongoing research will hopefully gradually improve the knowledge about this potentially devastating disease, and help us to develop better preventative strategies, diagnostic tests, and management strategies.