Challenging cases in internal medicine: Managing a dog with chronic pruritus and proteinuria - Veterinary Medicine
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Challenging cases in internal medicine: Managing a dog with chronic pruritus and proteinuria
The older dog in this case had severe dermatologic problems and polyuria and polydipsia. Diagnosing both its external and internal problems and determining if any relationship existed between the two presented a challenge.


VETERINARY MEDICINE


Treatment and follow-up

Because the urine protein:creatinine ratio had improved and the owner was reluctant to allow invasive testing, a renal biopsy was not performed. Without histopathologic examination of a renal biopsy, we could not provide a definitive diagnosis for the cause of the dog's proteinuria. The decrease in urine protein loss may have resulted from cessation of exogenous glucocorticoids and improvement in the inflammatory skin disease. Because the dog continued to have proteinuria (i.e. urine protein:creatinine ratio > 1) and the hypoalbuminemia had not resolved, we prescribed an angiotensin-converting enzyme inhibitor (enalapril maleate, 0.5 mg/kg orally once a day) to further reduce the proteinuria and perhaps slow the progression of chronic renal disease.6 Low-dose aspirin therapy (0.5 mg/kg orally once a day) was prescribed to ameliorate platelet-mediated glomerular inflammation and to reduce the thromboembolic tendency often associated with protein-losing renal disease.6,7 The referring veterinarian later prescribed carprofen for degenerative joint disease, so aspirin therapy was discontinued because of possible side effects when two nonsteroidal anti-inflammatory drugs are used. The dog was eating a premium-quality senior food, moderately restricted in protein, which was considered appropriate for this stage of the dog's renal disease.


Table 2: Urine Protein:Creatinine Ratios, Urinalysis Results, and Associated Skin Findings
Laboratory testing performed before the much-needed dentistry showed the dog's serum albumin concentration had increased to 2.5 g/dl and the blood urea nitrogen and creatinine concentrations remained normal. A urinalysis revealed 1+ protein, a specific gravity of 1.016, and a normal sediment. Table 2 summarizes urine testing results over time in this patient as they relate to the status of the skin disease. Although the proteinuria improved, it never resolved. It is not possible to assess the relative contribution of the enalapril vs. other aspects of the case management (e.g. treatment of demodicosis and bacterial pyoderma, cessation of glucocorticoid therapy) to the improvement in the proteinuria.

DISCUSSION

Adult-onset canine demodicosis presents in one of two patient populations. The first is a group of dogs with a history of demodicosis as a puppy or young adult. The disease either spontaneously resolves or is, apparently, successfully treated. These dogs remain clinically normal until something triggers a relapse later in life. It is speculated that these dogs develop initial disease because of an inherent defect in the skin's immune system. The second is a group of dogs with no known history of demodicosis as a puppy or young adult that develop disease for the first time as older adults (i.e. usually over 5 years of age).8

In this second group of dogs, or dogs with true adult-onset demodicosis, it is unclear what triggers the disease. Obviously, the host has been living in harmony with its Demodex mite population for years until something changes. The most commonly cited cause is an underlying medical condition that debilitates or immunocompromises the host (e.g. diabetes mellitus, hyperadrenocorticism, hypoadrenocorticism, excessive glucocorticoid administration, hypothyroidism, neoplasia). In many dogs, the underlying disease may not be apparent when the demodicosis is diagnosed. One of the authors (Dr. Moriello) has observed adult-onset demodicosis to precede the detection of a perianal adenocarcinoma by one year. That dog's demodicosis was unresponsive to medical treatment but resolved with surgical excision of the tumor a year later when it was discovered.

The diagnosis and treatment of adult-onset demodicosis is a two-step process. First, the demodicosis needs to be diagnosed, usually by skin scrapings. Multiple deep skin scrapings (> 5) are recommended. The most common cause of missing the diagnosis is to do too few skin scrapings. Although Demodex mites are a normal part of the skin's fauna, they are rarely found in skin scrapings from healthy dogs. So their presence on a skin scraping should alert you to a problem.8 Second, the underlying trigger for the adult-onset demodicosis needs to be investigated. This investigation can be difficult, expensive, and sometimes unrewarding.


Table 3: Treatment Considerations for Demodicosis
Treatment of adult-onset demodicosis is similar to that of juvenile demodicosis. Concurrent bacterial and yeast pyodermas should be treated for at least 30 days. If a deep pyoderma is present, delay topical therapy until it is healed. Clip the hair for easier medicated bathing (select a follicular flushing or an antimicrobial shampoo based on patient assessment) and, if and when appropriate, administer weekly amitraz dips. It is unclear which of the various treatments are most effective in dogs with generalized demodicosis, particularly adult-onset forms. A critical factor in treatment success is whether the underlying trigger can be identified and cured or at least managed. If not, then it is unlikely the demodicosis will be cured, and the dog's clinical signs will only be managed. Regardless of the treatment protocol, continue treatment for at least 30 days past mite cure (i.e. negative results for two skin scrapings at weekly or biweekly intervals). Treatment considerations for demodicosis are listed in Table 3.

Investigating the underlying cause of adult-onset demodicosis requires obtaining a thorough history. One of the authors (Dr. Moriello) had a canine patient whose adult-onset demodicosis was secondary to its owner's excessive application of a human prescription betamethasone ointment to the dog's skin. In other cases, the cause is more obvious (e.g. the dog has hypothyroidism or diabetes mellitus, or it has been receiving exogenous oral or injectable glucocorticoids). Dogs with adult-onset demodicosis may require extensive evaluation to identify the underlying cause of the mite overpopulation. This evaluation may include a complete blood count, a serum chemistry profile, urinalysis, urine cultures, thoracic and abdominal radiography and ultrasonography, ACTH stimulation testing, low-dose dexamethasone suppression testing, and a thyroid profile.

In this case, it was difficult to pinpoint what triggered and perpetuated the dog's adult-onset demodicosis. The dog may have had its usual episode of seasonal atopic dermatitis the previous fall and then developed a concurrent bacterial and yeast pyoderma. Inappropriate therapy may have led to a lack of clinical response, and glucocorticoid use may have triggered the adult-onset demodicosis. Because the dog had been acquired at 8 months of age, juvenile demodicosis cannot be ruled out. Also, the low albumin and elevated cholesterol concentrations and proteinuria must be considered. The skin requires a great deal of protein each day for homeostasis, and any protein loss from the body or decrease in protein production or daily intake will be reflected in the health of the skin.

A definitive cause for the chronic PU/PD was not ascertained. The finding of relatively concentrated urine (specific gravities of 1.035 and 1.026) on two separate occasions made the observation of PU/PD by the owner suspect; the problem may have been intermittent or associated with glucocorticoid use.

Although a histologic diagnosis of the kidney disease was not obtained, glomerulonephritis was tentatively diagnosed. The degree of elevation of the urine protein:creatinine ratio, probable exclusion of pyelonephritis (based on results of the urinalysis, urine culture, and renal ultrasonographic examination), and the finding of hypercholesterolemia are all consistent with glomerulonephritis. Glomerulonephritis can be idiopathic or result from infectious, inflammatory, or neoplastic disease. Although the only infectious diseases identified in this case were the periodontitis and the pyoderma, the chronicity and severity of these inflammatory processes could have been a source for antigen:antibody complexes that could result in secondary glomerulonephritis. Dogs with generalized demodicosis and recurrent staphylococcal pyoderma have been reported to have significantly higher mean circulating immune complexes compared with normal dogs.9 At least one breed of dog, the soft-coated wheaten terrier, which has a high incidence of protein-losing nephropathy, has also been noted to have an increased incidence of inflammatory skin disease (e.g. atopy, pyoderma), although the cause-and-effect relationship is unknown.10 Alternatively, a more global disorder of the immune system could have resulted in both the adult-onset demodicosis and the presumptive glomerulonephritis. Since a renal biopsy was not obtained, it is also possible that this dog had chronic interstitial nephritis of unknown cause with an unusual degree of proteinuria. But it would be unusual to find adequately concentrated urine in a dog with marked chronic interstitial nephritis (i.e. severe enough to cause proteinuria, hypoalbuminemia, and hypercholesterolemia). Whatever the renal diagnosis, the proteinuria in this case was exacerbated by glucocorticoid use or the deep pyoderma, since the proteinuria improved markedly with glucocorticoid discontinuation and appropriate treatment of the skin diseases, even before treatment with enalapril.

It is interesting to relate the urine protein:creatinine ratios to the presence or absence of skin disease (Table 2). The urine protein:creatinine ratio was at its highest when the dog was most symptomatic (i.e. untreated severe deep pyoderma and demodicosis). At this point the dog's prognosis seemed poor, and severe, irreversible, and worsening renal disease as an underlying trigger of the adult-onset demodicosis was discussed with the owner. It was surprising that the urine protein:creatinine ratio markedly improved and almost reached normal when the dog's skin disease was in remission. Interestingly, the urine protein:creatinine ratio worsened when the dog's skin disease relapsed. Clearly, it seems concurrent disease can affect this renal function test. An important lesson in this case is that decisions about treatment, prognosis, and, in particular, euthanasia, should be made only after obtaining several urine protein:creatinine ratio measurements, preferably after treating concurrent disease.

Adult-onset demodicosis and protein-losing kidney disease are serious disorders that carry poor prognoses. Fortunately, this dog responded well to therapy for both conditions, and the owner eventually allowed dentistry to address the periodontal disease. The improved quality of life certainly extended this dog's life, because the owners had been considering euthanasia because of the dog's discomfort from its skin problems. Alternatively, if the protein-losing renal disease had been allowed to progress, as it usually does without intervention, the dog might have succumbed to renal failure or a complication of the hypoproteinemia, such as a thromboembolic event.

Karen A. Moriello, DVM, DACVD
Melissa S. Wallace, DVM, DACVIM
Department of Medical Sciences
School of Veterinary Medicine
University of Wisconsin
Madison, WI 53706

REFERENCES

1. Center, S.A. et al.: 24-Hour urine protein/creatinine ratio in dogs with protein-losing nephropathies. JAVMA 187 (8):820-824; 1985.

2. Waters, C.B. et al.: Effects of glucocorticoid therapy on urine protein-to-creatinine ratios and renal morphology in dogs. J. Vet. Intern. Med. 11 (3):172-177; 1997.

3. Center, S.A. et al.: Clinicopathologic, renal immunofluorescent, and light microscopic features of glomerulonephritis in the dog: 41 cases (1975-1985). JAVMA 190 (1):81-90; 1987.

4. Cook, A.K.; Cowgill, L.D.: Clinical and pathological features of protein-losing glomerular disease in the dog: A review of 137 cases (1985-1992). JAAHA 32 (4):313-322; 1996.

5. Peterson, M.E. et al.: Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. JAVMA 211 (11):1396-1402; 1997.

6. Grauer, G.F. et al.: Effects of enalapril versus placebo as a treatment for canine idiopathic glomerulonephritis. J. Vet. Intern. Med. 14 (5):526-533; 2000.

7. Grauer, G.F.: Glomerulonephritis. Semin. Vet. Med. Surg. 7:187-197; 1992.

8. Scott, D.W. et al.: Canine demodicosis. Muller and Kirk's Small Animal Dermatology, 6th Ed. W.B. Saunders, Philadelphia, Pa., 2000; pp 457-476.

9. DeBoer, D.J. et al.: Circulating immune complex concentrations in selected cases of skin disease in dogs. AJVR 49 (2):143-146; 1988.

10. Littman, M.P. et al.: Familial protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers: 222 cases (1983-1997). J. Vet. Intern. Med. 14 (1):68-80; 2000.


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