Research
Research EDITORIAL
‘New Forest syndrome’: first pieces of the puzzle Stefano Cortellini and Karen Humm In the past two to three years, there has been much interest surrounding the apparent emergence of a disease commonly known to the general public as ‘New Forest syndrome’. There are many similarities between this disease and a disorder previously described in the USA, which was often referred to as ‘Alabama rot’, although there are differences in clinical presentation between this and New Forest syndrome (Carpenter and others 1988, Herzke and others 1995). It could be argued that both diseases should more correctly be named cutaneous and renal glomerular vasculopathy (CRGV) based on their histopathological features, rather than their geographic distribution. Many clients will have read articles in the popular press regarding New Forest syndrome and its high morbidity and mortality, leading to concerns which veterinary surgeons may have had difficulty addressing given the lack of information available other than anecdote. The article by Holm and others (2015), summarised on p 384 of this issue of Veterinary Record is therefore a major step forward, by both providing vets with information regarding presenting signs of affected animals and also by characterising the disease in more detail. The former aspect is obviously important, as we need to recognise dogs that may have CRGV. The main clinical features described are
Stefano Cortellini, DVM, MVetMed, DACVECC, MRCVS, Karen Humm, MA, VetMb, CertVA, DACVECC, DipECVECC, FHEA, MRCVS, Department of Veterinary Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK e-mail: [email protected]
382 | Veterinary Record | April 11, 2015
often vague, but cutaneous and/or oral lesions in conjunction with acute kidney injury (AKI) (either present on admission or which develops in the following days) should lead clinicians to consider the disease as a differential diagnosis. Characterisation of the disease is, however, arguably more important than describing the presenting signs. Holm and others have described the histopathological lesions seen in these cases, which will aid further research in the area, hopefully leading to an understanding of the cause of this CRGV outbreak, how to prevent the disease and the optimal method of treatment. A major strength of Holm and others’ study is that all cases were definitively diagnosed with CRGV via histopathology. However, the dogs included in the study were all diagnosed at postmortem examination, as there are concerns regarding the invasiveness of renal biopsy in patients with AKI (Ross 2011). Therefore, we do not currently know the spectrum of severity of the disease and what the survival rate of dogs with CRGV is. The authors of the study state that they strongly suspected CRGV in other dogs that survived. They also report that some dogs that had come into contact with the cases reported in the study developed skin lesions but not AKI (or at least AKI that was recognised), perhaps representing a less aggressive form of the disease. Biopsy of cutaneous lesions (as a less invasive option than renal biopsy) could be considered if the disease is suspected. Although this would not allow for the definitive diagnosis of CRGV, histopathological confirmation of vasculopathy in biopsy specimens from ulcerative skin lesions would support a presumptive diagnosis, in combination
Research with other compatible clinical findings. Unfortunately, sedation or general anaesthesia would probably be required, which is not desirable in an AKI patient. In the future hopefully less invasive methods of diagnosis will be developed, allowing us to increase our understanding of the disease, particularly why some patients survive and others do not. It is difficult to give recommendations for patients with cutaneous lesions resembling those seen in dogs with CRGV, especially as they are variable in appearance, meaning the disease will probably be suspected far more often than it is actually present. Monitoring creatinine in the days following unexplained cutaneous or oral lesions could be discussed with an owner, especially if there are other compatible clinical signs, and this may be advisable in those cases with signs of systemic involvement in order to detect renal dysfunction at an early stage of the process. CRGV has been reported in greyhounds in the USA, but few cases have been reported outside of that country or in different breeds (Herzke and others 1995, Rottermund and others 2002). No causative agent for the disease was identified in previously reported cases, although a genetic predisposition was suggested by Carpenter and others (1988). CRGV is a histopathological diagnosis and whether the dogs in these reports had the same disease process as those described by Holm and others is unclear. Certainly the marked limb bruising and oedema noted in the greyhounds with Alabama rot suggests there are differences in clinical presentation with the cases described by Holm and others (Carpenter and others 1988). Unfortunately, despite the admirable effort of Holm and others in searching for a cause for CRGV in the cases they describe, none was identified. Similar histopathological cutaneous and renal lesions are seen in people with haemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) (George andNeoter 2014), which may mean that
there are similarities in the pathogenesis of these conditions, although this is currently conjecture. As Holm and others suggest, further investigation in this direction could allow a cause or predisposing factor to be identified. Both the apparent seasonal presentation (winter and spring) and the concentration of affected dogs in the New Forest area in this case series should be helpful in aiding our understanding of a possible aetiology. However, given the potential for underdiagnosis of the disease, Holm and others quite correctly question whether CRGV is truly more prevalent in the New Forest area (or whether there is just increased awareness here), whether it is seasonal (as this data suggests) or indeed whether the disease is novel at all. Given the high number of canine AKI cases that do not have an underlying aetiology detected (Vaden and others 1997) it is possible that CRGV may have previously been an unrecognised cause. Because of the uncertain aetiology of this disease, neither the optimal prevention strategy nor treatment is known. Therapeutics from antibiosis to pentoxyfilline were used in the cases described. Fresh frozen plasma transfusions, plasma therapeutic exchange and monoclonal antibody therapy are discussed by Holm and others as possible therapies, given the similarities to the human diseases HUS and TTP noted above. However, no specific recommendations can be made regarding management at this point other than providing appropriate symptomatic care for AKI and cutaneous lesions. The article by Holm and others (2015) has provided us with a base from which to start studying CRGV in the UK. The investigation thus far has involved a huge amount of effort by many veterinary surgeons, which should be applauded. Collaboration between different referral institutes and general practitioners has allowed this information to be gathered and funding for testing has been generously donated. By increasing awareness of this
disease, Holm and others’s publication lays the foundation stone for further investigations to address this new diagnostic and therapeutic challenge that veterinary medicine must face.
References
Carpenter, J. L., Andelman, N. C., Moore, F. M. & Wing, N. W., Jr (1988) Idiopathic cutaneous and renal glomerular vasculopathy of greyhounds. Veterinary Pathology 25, 401-407 George, J. N. & Nester, C. M. (2014) Syndromes of thrombotic microangiopathy. New England Journal of Medicine 371, 654-66 Herzke, D. M., Cowan, L. A., Schoning, P. & Fenwick B. W. (1995) Glomerular ultrastructural lesions of idiopathic cutaneous and renal glomerular vasculopathy of greyhounds. Veterinary Pathology 32, 451-459 Holm, L. P., Hawkins, I., Robin, C., Newton, R. J., Jepson, R., Stanzani, G., McMahon, L. A. & others (2015) Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK. Veterinary Record doi: 10.1136/vr.102892 Ross, L. (2011) Acute kidney injury in dogs and cats. Veterinary Clinics of North America: Small Animal Practice 41, 1-14 Rotermund, A., Peters, M., HewickerTrautwein, M. & Nolte, I. (2002) Cutaneous and renal glomerular vasculopathy in a great dane resembling ‘Alabama rot’ of greyhounds. Veterinary Record 151, 510-512 Vaden, S. L., Levine, J. & Breitschwerdt, E. B. (1997) A retrospective case-control of acute renal failure in 99 dogs. Journal of Veterinary Internal Medicine 11, 58-64
doi: 10.1136/vr.h1802
April 11, 2015 | Veterinary Record | 383
Copyright of Veterinary Record: Journal of the British Veterinary Association is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Research EDITORIAL
‘New Forest syndrome’: first pieces of the puzzle Stefano Cortellini and Karen Humm In the past two to three years, there has been much interest surrounding the apparent emergence of a disease commonly known to the general public as ‘New Forest syndrome’. There are many similarities between this disease and a disorder previously described in the USA, which was often referred to as ‘Alabama rot’, although there are differences in clinical presentation between this and New Forest syndrome (Carpenter and others 1988, Herzke and others 1995). It could be argued that both diseases should more correctly be named cutaneous and renal glomerular vasculopathy (CRGV) based on their histopathological features, rather than their geographic distribution. Many clients will have read articles in the popular press regarding New Forest syndrome and its high morbidity and mortality, leading to concerns which veterinary surgeons may have had difficulty addressing given the lack of information available other than anecdote. The article by Holm and others (2015), summarised on p 384 of this issue of Veterinary Record is therefore a major step forward, by both providing vets with information regarding presenting signs of affected animals and also by characterising the disease in more detail. The former aspect is obviously important, as we need to recognise dogs that may have CRGV. The main clinical features described are
Stefano Cortellini, DVM, MVetMed, DACVECC, MRCVS, Karen Humm, MA, VetMb, CertVA, DACVECC, DipECVECC, FHEA, MRCVS, Department of Veterinary Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK e-mail: [email protected]
382 | Veterinary Record | April 11, 2015
often vague, but cutaneous and/or oral lesions in conjunction with acute kidney injury (AKI) (either present on admission or which develops in the following days) should lead clinicians to consider the disease as a differential diagnosis. Characterisation of the disease is, however, arguably more important than describing the presenting signs. Holm and others have described the histopathological lesions seen in these cases, which will aid further research in the area, hopefully leading to an understanding of the cause of this CRGV outbreak, how to prevent the disease and the optimal method of treatment. A major strength of Holm and others’ study is that all cases were definitively diagnosed with CRGV via histopathology. However, the dogs included in the study were all diagnosed at postmortem examination, as there are concerns regarding the invasiveness of renal biopsy in patients with AKI (Ross 2011). Therefore, we do not currently know the spectrum of severity of the disease and what the survival rate of dogs with CRGV is. The authors of the study state that they strongly suspected CRGV in other dogs that survived. They also report that some dogs that had come into contact with the cases reported in the study developed skin lesions but not AKI (or at least AKI that was recognised), perhaps representing a less aggressive form of the disease. Biopsy of cutaneous lesions (as a less invasive option than renal biopsy) could be considered if the disease is suspected. Although this would not allow for the definitive diagnosis of CRGV, histopathological confirmation of vasculopathy in biopsy specimens from ulcerative skin lesions would support a presumptive diagnosis, in combination
Research with other compatible clinical findings. Unfortunately, sedation or general anaesthesia would probably be required, which is not desirable in an AKI patient. In the future hopefully less invasive methods of diagnosis will be developed, allowing us to increase our understanding of the disease, particularly why some patients survive and others do not. It is difficult to give recommendations for patients with cutaneous lesions resembling those seen in dogs with CRGV, especially as they are variable in appearance, meaning the disease will probably be suspected far more often than it is actually present. Monitoring creatinine in the days following unexplained cutaneous or oral lesions could be discussed with an owner, especially if there are other compatible clinical signs, and this may be advisable in those cases with signs of systemic involvement in order to detect renal dysfunction at an early stage of the process. CRGV has been reported in greyhounds in the USA, but few cases have been reported outside of that country or in different breeds (Herzke and others 1995, Rottermund and others 2002). No causative agent for the disease was identified in previously reported cases, although a genetic predisposition was suggested by Carpenter and others (1988). CRGV is a histopathological diagnosis and whether the dogs in these reports had the same disease process as those described by Holm and others is unclear. Certainly the marked limb bruising and oedema noted in the greyhounds with Alabama rot suggests there are differences in clinical presentation with the cases described by Holm and others (Carpenter and others 1988). Unfortunately, despite the admirable effort of Holm and others in searching for a cause for CRGV in the cases they describe, none was identified. Similar histopathological cutaneous and renal lesions are seen in people with haemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) (George andNeoter 2014), which may mean that
there are similarities in the pathogenesis of these conditions, although this is currently conjecture. As Holm and others suggest, further investigation in this direction could allow a cause or predisposing factor to be identified. Both the apparent seasonal presentation (winter and spring) and the concentration of affected dogs in the New Forest area in this case series should be helpful in aiding our understanding of a possible aetiology. However, given the potential for underdiagnosis of the disease, Holm and others quite correctly question whether CRGV is truly more prevalent in the New Forest area (or whether there is just increased awareness here), whether it is seasonal (as this data suggests) or indeed whether the disease is novel at all. Given the high number of canine AKI cases that do not have an underlying aetiology detected (Vaden and others 1997) it is possible that CRGV may have previously been an unrecognised cause. Because of the uncertain aetiology of this disease, neither the optimal prevention strategy nor treatment is known. Therapeutics from antibiosis to pentoxyfilline were used in the cases described. Fresh frozen plasma transfusions, plasma therapeutic exchange and monoclonal antibody therapy are discussed by Holm and others as possible therapies, given the similarities to the human diseases HUS and TTP noted above. However, no specific recommendations can be made regarding management at this point other than providing appropriate symptomatic care for AKI and cutaneous lesions. The article by Holm and others (2015) has provided us with a base from which to start studying CRGV in the UK. The investigation thus far has involved a huge amount of effort by many veterinary surgeons, which should be applauded. Collaboration between different referral institutes and general practitioners has allowed this information to be gathered and funding for testing has been generously donated. By increasing awareness of this
disease, Holm and others’s publication lays the foundation stone for further investigations to address this new diagnostic and therapeutic challenge that veterinary medicine must face.
References
Carpenter, J. L., Andelman, N. C., Moore, F. M. & Wing, N. W., Jr (1988) Idiopathic cutaneous and renal glomerular vasculopathy of greyhounds. Veterinary Pathology 25, 401-407 George, J. N. & Nester, C. M. (2014) Syndromes of thrombotic microangiopathy. New England Journal of Medicine 371, 654-66 Herzke, D. M., Cowan, L. A., Schoning, P. & Fenwick B. W. (1995) Glomerular ultrastructural lesions of idiopathic cutaneous and renal glomerular vasculopathy of greyhounds. Veterinary Pathology 32, 451-459 Holm, L. P., Hawkins, I., Robin, C., Newton, R. J., Jepson, R., Stanzani, G., McMahon, L. A. & others (2015) Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK. Veterinary Record doi: 10.1136/vr.102892 Ross, L. (2011) Acute kidney injury in dogs and cats. Veterinary Clinics of North America: Small Animal Practice 41, 1-14 Rotermund, A., Peters, M., HewickerTrautwein, M. & Nolte, I. (2002) Cutaneous and renal glomerular vasculopathy in a great dane resembling ‘Alabama rot’ of greyhounds. Veterinary Record 151, 510-512 Vaden, S. L., Levine, J. & Breitschwerdt, E. B. (1997) A retrospective case-control of acute renal failure in 99 dogs. Journal of Veterinary Internal Medicine 11, 58-64
doi: 10.1136/vr.h1802
April 11, 2015 | Veterinary Record | 383
Copyright of Veterinary Record: Journal of the British Veterinary Association is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
