URINARY INCONTINENCE IN DOGS AND CATS

Urinary incontinence is a disorder of micturition characterized by involuntary escape of urine during the storage phase of urinary cycle. The most common presentation is intermittent or continuous dribbling of urine combined with episodes of normal voiding.

Pathophysiology

Micturition depends on the coordinated actions among the sympathetic, parasympathetic, and somatic nervous systems and central control centers. The coordination between these systems takes place in the pontine micturition center (PMC), also known as Barrington’s nucleus, which is located in the dorsomedial pontine tegmentum in the brainstem. The PMC receives input from other sensory stimuli to determine the onset of micturition.

The urinary cycle is divided into two phases: the filling phase, and the emptying phase. The sympathetic innervation, supplied by the hypogastric nerve, regulates the filling phase. The Sympathetic preganglionic fibers exit the lumbar spinal cord (L1-L4 in dogs and L2-L5 in cats) and synapse in the caudal mesenteric ganglia. Postganglionic fibers (hypogastric nerve) release norepinephrine (NE) to activate β-receptors in the body of the bladder, resulting in relaxation and stretching, while stimulation of α-receptors in the trigone region and proximal urethra causes constriction. In addition, the sympathetic stimulation inhibits urination by blocking parasympathetic transmission.

As the bladder fills, sensory receptors embedded in the bladder wall become activated. Information from these receptors travels via the pelvic nerve to the spinal cord, where the information is relayed to the PMC of the brain stem. The PMC determines the onset of micturition.

The Parasympathetic preganglionic motor neurons arise from the sacral spinal cord segments S1 to S3. Preganglionic fibers travel in the pelvic nerve and synapse in the peripheral ganglia in the wall of the bladder. Short postganglionic fibers provide excitatory input to the bladder through ACh acting on cholinergic (muscarinic) receptors in the bladder and also provide inhibitory input to the urethra, thus facilitating voiding. The pudendal nerve is simultaneously inhibited, allowing relaxation of the external urethral sphincter.

Somatic innervation, supplied via the pudendal nerve, also arises from the sacral spinal cord segments S1 to S3 and provides stimulation (via ACh on nicotinic receptors) to the external urethral sphincter, an area of striated muscle. Cell bodies of this nerve are located in the ventrolateral nucleus of Onuf.

Urinary incontinence (UI) refers to unconscious voiding of urine, whereas consciously voiding small amounts of urine in inappropriate locations (pollakiuria is referred to as urge incontinence.

Conditions causing incontinence

1.      Urethral Sphincter Mechanism Incompetence (USMI)

USMI usually occurs in spayed female dogs, but can occur in intact females and male dogs as well. In spayed females, the onset usually starts 2 to 3 years after an uneventful spay but can occur weeks to years after an ovariohysterectomy. Nocturia appears to be the most common complaint from owners. UI can be daily or episodic and can range from mild to very severe. The incidence is 5.1% to 9.7% of spayed dogs. If only large-breed dogs are considered, the incidence approaches 12.5% of spayed females.

It has been theorized that because estrogen exerts a permissive effect on the α-receptors of the internal urethral sphincter, removal of estrogen results in decreased responsiveness of the muscle to sympathetic stimulation and decreased internal sphincter tone.

Although urethral incompetence occasionally occurs in male dogs, it has not been definitively associated with castration. However, a definitive diagnosis can be obtained only by urodynamic tests. A urethral pressure profile (UPP) evaluates the pressure along the entire length of the urethra; a cystometrogram evaluates the detrusor reflex, bladder fill volumes, and compliance.

Medical management of USMI includes the use of drugs aimed at improving urethral pressures via the α1-adrenoceptors (α1-AR), such as phenylpropanolamine (PPA). The therapeutic benefit is usually seen within 2 to 3 days. The oral dosage is 1 to 2 mg/kg PO q8-12h. Adverse effects in dogs receiving α-agonists can include restlessness, anxiety, hypertension, increased intraocular pressure and hepatic glycogenolysis. PPA is not recommended for patients with cardiac disease, hypertension, kidney disease, glaucoma, or diabetes mellitus.  If required for dogs with kidney disease, lower dosages should be administered and the patient’s blood pressure should be monitored regularly, ideally 2 to 4 hours post–PPA administration.

In cases that do not respond adequately to α-adrenergic agonists, combination therapy with estrogen supplementation can be attempted. Both drugs should initially be given at the recommended dose; if the drugs are effective, the α-agonist should be reduced to the lowest effective dose. Estrogens are thought to sensitize the α1-AR to NE and indirectly result in an improvement in the closure pressure, but the exact mechanism of action of these drugs is unclear. Diethylstilbestrol (DES) is a synthetic estrogen that has been successfully used to treat spay-related incontinence. The oral dosage is 0.5-1.0 mg/dog PO q24h for 3 to 5 days, then q7d. Adverse effects include vulvar or mammary swelling, attractiveness to males, lethargy, vomiting, and diarrhea. It causes prostatic metaplasia in males. Although estrogens can lead to bone marrow suppression, this has not been reported at recommended doses. DES shouldn’t be used in cats and intact female dogs. Another estrogen compound, Estriol can also be used for the medical management of USMI. The oral dosage is 2 mg/dog PO q24h for 14 days, then reduced in 0.5-mg increments q7d to lowest effective dose. A complete blood count (CBC) should be monitored periodically in all dogs receiving estrogen therapy.

Imipramine, a tricyclic antidepressant, inhibits norepinephrine reuptake at the neuronal synapse, thereby increasing sympathetic tone. Although this drug may be useful in treating refractory cases of sphincter incompetence, there has been little research to document its effectiveness. Potential side effects, including sedation, aggression, constipation, hypotension, and tachycardia, may limit its use. The oral dosage for dogs is 5-15 mg/dog PO q12h and the oral dosage for cats is 2.5-5 mg/cat PO q12h.

Colposuspension is a procedure in which the urethra and vagina are surgically moved cranially so that the bladder neck is relocated to an intraabdominal position. Reported long-term continence rates for this surgery range from 13% to 53%, although a significantly larger percentage of owners reported partial relief from urine dribbling. Submucosal urethral bulking agent such as polydimethylsiloxane is available for animals that are refractory to medications. In this procedure, dogs are anesthetized and three to four deposits of the bulking agent are injected in a circular fashion approximately 1.5 cm distal to the trigone via the cystoscope. If dogs are nonresponsive to medical therapy, urethral occluders can also be considered. The occluders can be surgically placed around the proximal third of the urethra; they act as an external occluder to maintain continence. 

1.      Ectopic Ureter (EU)

Ureteral ectopia is a congenital abnormality characterized by termination of one or both ureters at a point distal to the bladder neck. The flow of urine bypasses the bladder neck, and affected animals typically leak urine from birth. In cases of unilateral ectopic ureter, normal urine voiding is reported because one ureter is properly emptying into the bladder. In bilateral cases, normal urination may not occur. Eighty percent to 89% of canine ectopic ureters occur in females, and at least one-quarter of these cases are bilateral.  Although ectopic ureters have been reported in cats, they are probably rare. Breeds such as soft coated wheaten terriers, Labrador & Golden retrievers, Siberian husky, English bulldog and Newfoundland have an increased incidence of ectopic ureters. Dogs with ectopic ureters often have urinary incontinence prior to neutering, although this may be misinterpreted as poor housetraining by the owners. EUs are uncommon in male dogs and, if present, affected patients may have few or no clinical signs or present with clinical signs at an older age. EUs are extremely rare in cats.

A diagnosis of EUs can be made by excretory urography, fluoroscopic urethrography or ureterography, abdominal ultrasonography, cystoscopy, helical computed tomography (CT), or a combination of these diagnostic procedures. The latter two are reported to be the most sensitive diagnostics for confirming the presence of EUs. Complete continence is achieved after surgical correction in approximately 65% of cases. It has been reported that dogs weighing less than 20 kg have a better outcome postoperatively.

2.      Overactive bladder (OAB) / Detrusor instability

Detrusor instability (hyperspasticity) is characterized by sudden awareness of an urgency to urinate combined with an involuntary bladder contraction. Clinical presentation includes nocturia, pollakiuria, urgency, and incontinence. Instability secondary to infection, neoplasia, or uroliths is called urge incontinence.  In some cases, an underlying inflammatory condition is not found and the condition is referred to as idiopathic detrusor instability. The first step in the diagnosis of this condition involves ruling out an underlying cause. As with all cases of urinary incontinence, thorough physical and neurologic examinations and patient history are essential. Urinalysis with microscopic analysis and culture is also vital, as is ultrasonography of the bladder wall and contents. Definitive diagnosis of idiopathic detrusor instability involves conducting cystometrography.

Oxybutynin is an anticholinergic agent that may help stop bladder spasms and promote urine retention. The oral dosage in dogs is 0.2 mg/kg PO q8-12h. The oral dosage in cats is 0.5-1.25 mg/cat PO q8-12h. Adverse effects may include diarrhea, constipation, hypersalivation, urine retention, and sedation. It should be used with caution in patients with hypotension.

A tricyclic antidepressant drug, Imipramine may increase bladder relaxation. Imipramine is considered for dogs that have urge incontinence secondary to behavioral problems. However, it should only be used when behavioral modifications have been unsuccessful, and discontinued when clinical signs improve.

1.      Other conditions causing incontinence

Malposition of the urinary bladder within the pelvis (i.e., “pelvic bladder”) is often associated with urinary incontinence. The bladder is ordinarily positioned in the abdomen. In affected patients, the bladder neck and some portions of the body are located in the pelvic canal. It is not clear why 50% of dogs with this condition are incontinent. This condition usually occurs in large-breed female dogs, although it has also been reported in males. Contrast radiography typically shows an abnormally shaped bladder that fails to taper at the junction with the urethra, which is displaced caudally in the pelvic canal. Empirical treatment with phenylpropanolamine is thought to be helpful but unlikely to result in total resolution of signs. Some have recommended colposuspension in cases in which medical management is unrewarding.

Urovaginal and urethrorectal fistulas are uncommon causes of incontinence in dogs. Urovaginal fistula has been documented as a complication of ovariohysterectomy and occurs secondary to entrapment of the distal ureter by a ligature. Diagnosis is sometimes possible with intravenous urography but may require more invasive techniques, such as antegrade ureterography. Urethrorectal fistula may be congenital or the result of trauma. Although English bulldogs may have a genetic predisposition to develop the congenital form of this condition, it has been described in other breeds. Dogs with urethrorectal fistula typically present with persistent UTIs and passage of urine from the anus. The diagnosis can be made by cystography or retrograde urethrography under fluoroscopy. Successful surgical correction of both urovaginal and urethrorectal fistulas has been described.

Male dogs with urinary incontinence pose a more difficult challenge. Although a less common problem in males, less than 50% of male dogs respond to medical therapy, and the most successful treatment is PPA. One possible reason for this is misdiagnosis of dogs with USMI when in fact they have overflow incontinence from urethral sphincter dyssynergia or functional urethral obstruction. Measurement of a residual urine volume is essential to rule this out. Testosterone cypionate has had some anecdotal use in males with USMI and may provide some improvement. Testosterone is thought to improve urethral smooth muscle tone. The dosage of testosterone cypionate in dogs is 2.2 mg/kg IM q30-60 d. Should be used with caution in patients with hepatic, cardiac or renal disease. The adverse effects include perineal adenoma and prostate enlargement. Urethral bulking agents may be placed antegrade through a cystotomy incision; however, there has not been formal evaluation of this procedure and its overall success rate is unknown.

A persistent increase in urethral closure pressure from a mechanical or functional obstruction can lead to secondary bladder dysfunction (atony) and overflow incontinence. Mechanical causes for urinary retention include urethroliths, bladder and/or urethral neoplasia, proliferative urethritis, urethral strictures and foreign bodies, urethral plugs, prostatic diseases (e.g., abscess, paraprostatic cyst, benign prostatic hypertrophy), and extraluminal urethral compressions. Functional obstructions can be seen with supra-sacral or brainstem disease (upper motor neuron bladders), urethral spasms that usually occur secondary to urethritis or a mechanical obstruction, and idiopathic functional urethral outflow tract obstruction, also known as detrusor-urethral dyssynergia (reflex dyssynergia). The diagnosis of overflow incontinence is made based on history, thorough physical and neurologic examination, and complete imaging of the urinary tract. Most animals will have a history of intermittent to persistent stranguria prior to the UI. Watching the animal void and assessing the residual urine volume is also helpful. Normal animals will have less than 0.5 to 1 mL/kg of urine remaining in the bladder after voiding. Plain radiography, cystourethrography, and cystoscopy can all be beneficial to evaluate the patient for mechanical obstructions.

The diagnosis of idiopathic functional urethral outflow tract obstruction (detrusor-urethral dyssynergia) is usually made when all other causes for the increased urethral closure pressure have been excluded. This disease usually occurs in large-breed male dogs, both castrated or intact. Treatment for mechanical obstructions is to remove the obstruction, if possible. Urethral stones can be removed via surgery or holmium: YAG laser lithotripsy. Bladder and urethral neoplasia, usually transitional cell carcinoma (TCC), should be treated with piroxicam or another nonsteroidal anti-inflammatory drug (NSAID); other chemotherapeutics such as mitoxantrone or platinum compounds may improve survival.

For idiopathic, functional, urethral outflow tract obstruction, α1-adrenoceptor antagonists such as prazosin can be used to help relax the internal urethral sphincter. The dosage of prazosin in dogs is 1 mg/dog PO q8-12h for dogs weighing less than 15 kg and 2 mg/dog PO q8-12h for dogs weighing more than 15 kg. The dosage in cats is 0.25-1 mg/cat PO q8-12h.

Tamsulosin is useful in treating ureterospasm associated with ureteritis or ureteroliths. Tamsulosin is a selective α1a-adrenergic blocker that is more selective to the urinary tract (i.e., prostatic urethra, bladder neck) and thus has more limited cardiovascular side effects. The dosage in dogs is 0.1-0.2 mg/10 kg (up to 0.4-mg total dose) PO q12-24h. The dosage in cats is 0.004-0.006 mg/kg PO q12-24h.

Parasympathomimetics can be started if secondary bladder atony is also present. Bethanechol, a cholinergic agent, that directly stimulates muscarinic receptors in the detrusor smooth muscle of the bladder. can help restore bladder tone and facilitate bladder emptying. The dosage in dogs is 2.5-25 mg/dog PO q8h. The dosage in cats is 1.25-7.5 mg/cat PO q8h.  In severe cases, a tube cystotomy, indwelling urinary catheter, or urethral stent may be needed for urine evacuation.

Conclusion

Urinary incontinence can be frustrating for the animal owners. Fortunately, its easy to diagnose in most cases and managed medically. Few cases may require intensive measures.

 

1.

References

1. Acierno, Mark J., and Mary Anna Labato. "Canine incontinence." Compendium 28.8 (2006).

2.      Byron, Julie. "Canine Urinary Incontinence." American Veterinarian 3.5 (2018).

3.     Drippy Dogs: Causes and Treatment of Urinary Incontinence by Julie K. Byron, DVM, MS, DACVIM (NAVC Conference 2014 Small Animal)

4.    Drugs used to treat urinary incontinence in dogs and cats by Julie K. Byron, DVM, MS, DACVIM (Plumbs Therapeutic Brief, 2017).

5.     Nelson, Richard W., and C. Guillermo Couto. Small animal internal medicine-E-book. Elsevier Health Sciences, 2019.

 

CANINE ATOPIC DERMATITIS (AD)

Introduction

Canine atopic dermatitis (AD) is genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE antibodies most commonly directed against environmental allergens. Canine atopic-like dermatitis (ALD) describes an inflammatory and pruritic skin disease with clinical features identical to those seen in CAD; however, an IgE response to environmental or other allergens cannot be documented.

 Patients prone to IgE-mediated allergic reactions are said to be atopic. Atopic dermatitis is experienced by 3 % to 15% of the general canine population. Cutaneous exposure is believed to be the most important route of exposure; inhaled/ingested allergens may play some role in lesion development.

Signalment

Clinical signs typically begin at 6 months to 3 years of age. There is no sex predisposition. The following breeds were most commonly reported; West highland white terriers, Labrador and golden retrievers, German shepherd dogs, boxers, Dalmatian, Shar-peis, and French and English bulldogs. Depending on the allergens involved, the disease may be seasonal, non-seasonal or non-seasonal with seasonal flares.

Etiology and Pathogenesis

The environmental proteins to which the body overreacts or reacts in an abnormal manner are called allergens and include pollens, molds, dusts, danders, mites, and, in some cases, insects, chemicals, and foods.  

Canine atopic dermatitis (AD) is a dynamic disease and different mediators play a role at different times in the course of the reaction. The pathogenesis of atopy is mediated by numerous genetic as well as environmental factors (Fig 1). The disease process starts with percutaneous exposure and absorption of allergens through an epidermis that may have a defective barrier function.

1.       The naïve Langerhans cell captures and internalizes allergens. Allergens are then processed, packaged in major histocompatibility complex molecules on the Langerhans cell surface, and presented to naïve T-helper cells (Th0) cells in the draining lymph node. Specific cues from the microenvironment enable dendritic cells to activate T-helper cells and polarize them toward a Th2 phenotype.

2.       Th2 cells produce cytokines such as IL-4 and IL-13. These cytokines can stimulate B cells to become plasma cells that begin producing allergen-specific IgE.

3.       Activated Th2 cells migrate to the skin with the help of chemokines produced by various cells in the skin. Allergen specific IgEs also enter into the circulation and other tissues and bind to cells expressing high- and low-affinity Fcε receptors on their cell surface.

4.       Upon re-exposure to the same allergen, the epidermal Langerhans cell with cell surface–bound allergen-specific IgE efficiently binds the allergen and migrates to the dermis. These Langerhans cells then present the allergen to T-helper lymphocytes and continue to polarize them toward a Th2 phenotype. Additional Th2 cytokines such as IL-31 can be released and activate the sensory neuron to induce pruritus.

5.       Allergens can also cross-link allergen-specific IgE bound on the cell surface of dermal mast cells and stimulate the release of preformed inflammatory mediators such as histamine, serotonin, and substance P along with cytokines such as eosinophil chemotactic factor. Skin injury by scratching, microbial toxins from Staphylococcus sp and Malassezia sp, or environmental allergens activate keratinocytes and other innate immune cells to release pro-inflammatory cytokines (eg, IL-12) and chemokines that can polarize T-helper cells toward a Th1 phenotype, where they produce cytokines such as interferon (IFN)-γ.

6.      
In turn, IFN-γ promotes monocyte-macrophage cell activation. Activated keratinocytes, monocytes, and mast cells produce additional pro-inflammatory cytokines such as tumour necrosis factor (TNF)-α, upregulating the expression of P-selectin and E-selectin, on endothelial cells, thus recruiting more leukocytes from the blood. The epidermis thickens as does the stratum corneum; the barrier function worsens, allowing increased allergen penetration; and the cycle is perpetuated.

Clinical signs

The pruritus ranges from mild to severe. Erythematous macules, patches and micro papules (1-2 mm) consists the primary lesions of this disease. Excoriations, self-induced alopecia, lichenification (increased thickening), and scaling are the lesions that reflect chronic inflammation and self-trauma. As dogs with AD are predisposed to develop both superficial pyoderma and Malassezia dermatitis, lesions of bacterial folliculitis, exfoliative superficial pyoderma (epidermal collarettes) or seborrheic dermatitis can be present in addition to typical atopic skin lesions.  In most dogs with AD, the lesions are present in a characteristic distribution, and they are often bilaterally-symmetrical (Fig 2).

·       On the face, the lesions are visible on concave pinnae and the lips. The presence of periocular erythema, alopecia and lichenification reflects the presence of an associated allergic blepharo-conjunctivitis, a common occurrence.

·       On the trunk, lesions tend to affect areas of friction with poor hair coverage, such as the axillae, flanks, inguinal fold and lower abdomen. The ventral neck, perineum, perianal and ventral aspect of the tail are also commonly involved.

·       On the limbs, lesions clearly affect flexural aspects of the joints, such as those of the elbows, carpi, knees and hocks. Limb lesions are more medially than laterally distributed.

·       The feet most commonly harbour lesions, either in the dorsal interdigital space, or the ventral or dorsal metacarpi and metararsi. Between the footpads, lesions are often very edematous.

·       An otitis externa accompanies some 80% of the cases, and occasionally can be the main presenting sign. It commences by affecting the inner surface of the pinnae, auditory orifices and the vertical ear canals, but in longstanding cases the horizontal ear canals also become involved with a secondary infection involving bacteria and/or the yeast Malassezia.

·       Sneezing, reverse sneezing and rhinorrhoea in conjunction with cutaneous lesions likely herald the presence of associated allergic rhinitis. This can lead to profound facial pruritus in some dogs.  In contrary to the human atopic diseases, concurrent allergic asthma is a rare diagnosis made in dogs with AD.

Table 1. Additional body sites involved in canine AD in certain breeds

Breed	Location
Dalmatian French bulldogs German shepherd dog Boxer Shar-pei West Highland white terrier (WHWT)	Lips Eyelids, flexure surfaces Elbows, hind limbs, thorax Ears Thorax, flexure surfaces, dorso-lumbar area Dorso-lumbar area, lip, flexure surfaces

 

 Table 3. Key dermatological features for canine pruritic skin diseases

Alesional Pruritus	May be seen in the early stages of allergy or when seasonal disease begins. This finding of pruritus in areas with no lesions can occur in canine AD cases at any point in the disease process, especially in cases that have recurrences or come out of remission.
Primary skin lesions
Erythema	Can be seen with most of the above differentials, but lice and Cheyletiella do not usually cause erythema. Demodicosis is highly variable – the skin may or may not appear to be inflamed.
Papules	Seen with flea bites, scabies, Trombiculiasis, insect bite hypersensitivity, staphylococcal pyoderma, atopic dermatitis, cutaneous adverse food reaction, and contact dermatitis. Dogs with AD may have small non-crusted papules unless there are concurrent diseases.
Pustules	Most commonly associated with staphylococcal pyoderma
Secondary skin lesions
Epidermal collarettes	Most commonly associated with staphylococcal pyoderma
Crusting	Most commonly associated with secondary infections and excoriations
Salivary staining	Indicates excessive licking and often associated with Malassezia
Excoriations	Self-induced trauma from scratching due to severe pruritus
Alopecia	May be due to self-trauma or folliculitis (superficial pyoderma, demodicosis, and dermatophytosis)
Lichenification	Indicates chronic pruritus, inflammation and commonly associated with secondary infections
Hyperpigmentation	Indicates chronic pruritus. Allergies and Malassezia are the most common causes and result dark discoloration of the skin. Blue-grey pigmentation is seen with demodicosis in some cases.

 Diagnosis

The diagnosis of canine AD is made principally from a compatible signalment, suggestive history, and characteristic pruritus and clinical distribution.

International Committee for Allergic Diseases in Animals (ICADA) developed a set of practical guidelines that can be used to assist practitioners and researchers in the diagnosis of CAD. These guidelines provide an overview of the diagnosis of canine AD that involves three distinct, but complementary, approaches. These are:

1. Ruling out of other skin conditions with clinical signs that can resemble, or overlap with CAD. This is traditionally referred to as “the work-up”.

2. Detailed interpretation of the historical and clinical features of the condition. A new tool to assist with interpretation of these findings is the application of clinical criteria known as “Favrot’s criteria”.

3. Assessment of skin reactivity by Intradermal Testing (IDT) or detection of IgE by Allergen-Specific IgE Serology (ASIS) testing. This is traditionally referred to as “allergy testing”.

1.      Ruling out of other skin conditions with clinical signs that can resemble, or overlap with canine AD.

·       Consider the possibility of fleas (flea allergy dermatitis).

·       Consider the possibility of other ectoparasites (scabies, demodicosis, trombiculosis, otoacariasis, cheyeltiellosis).

·       Consider the possibility of Staphylococcal pyoderma and Malassezia dermatitis.

·       Consider the role of cutaneous adverse food reaction (CAFR). A strict elimination diet trial should be fed exclusively for a minimum of 8 weeks to achieve complete clinical remission in most cases.

·       Consider the possibility of contact dermatitis.

·       Consider the possibility of cutaneous/epitheliotropic lymphoma.

 

2.      Detailed interpretation of the historical and clinical features of canine AD

·       The initial clinical feature of canine AD is pruritus, which can include scratching, rubbing, chewing, excessive grooming or licking, scooting, and/or head shaking. Depending on the allergens involved, the pruritus may be seasonal (e.g., pollen) or non-seasonal (e.g., dust mites, food).

·       A new tool to assist with the interpretation of the clinical findings when confronted with a pruritic dog is application of clinical criteria known as “Favrot’s criteria” (Table 4). These include a set of criteria that have been developed from a large case series of confirmed cases of canine AD. The use of complex statistical analysis allowed a set of clinical features to be identified that had maximum association with canine AD. The analysis revealed two sets of criteria, which yield varying levels of sensitivity and specificity for the condition. Clinicians can use whichever set best serves their needs.

Table 2. Important differential diagnoses of pruritic skin diseases in dogs

Ectoparasitic skin diseases	Fleas Scabies (Sarcoptes scabie) Demodicosis Cheyletiellosis Otoacariasis (Otodectes cynotis) Trombiculiasis Nasal mites (Pneumonyssus caninum)
Microbial skin infections	Staphylococcal pyoderma Malassezia dermatitis
Allergic skin diseases	Flea allergy dermatitis Atopic dermatitis  Food intolerance/allergy Insect bite hypersensitivity Contact dermatitis
Neoplastic disease	Cutaneous lymphoma

 

Table 4. Favrot’s criteria

Use		Reliability
Set 1:	·       Use for clinical studies and adapt required criteria based on the goal of the study ·       If higher specificity is required, 6 criteria should be fulfilled (e.g., drug trails with potential side effects) ·       If higher sensitivity is required, 5 criteria should be fulfilled (e.g., epidemiological studies)	·       5 criteria: Sens. 85.4% Spec. 79.1%   ·       6 criteria: Sens. 77.2% Spec. 88.5%
1.       Age at onset <3 years 2.       Mainly indoor 3.       Corticosteroid responsive pruritus 4.       Chronic or recurrent yeast infections 5.       Affected front feet 6.       Affected ear pinnae 7.       Non-affected ear margins 8.       Non-affected dorso-lumbar area
Set 2:	·       Use to evaluate the probability of the diagnosis of  canine AD ·       5 criteria should be fulfilled ·       Do not use alone for the diagnosis of canine AD, and rule out resembling diseases	·       5 criteria: Sens. 85.4% Spec. 83%   ·       6 criteria: Sens. 42% Spec. 93.7%
1.       Age at onset <3 years 2.       Mainly indoor 3.       “Alesional” pruritus at onset 4.       Affected front feet 5.       Non-affected ear margins 6.       Non-affected dorso-lumbar area

 1.      Allergy testing

·       Once a clinical diagnosis of canine AD has been made several factors may play a role in the decision-making whether an allergy test is necessary or not. Severe clinical signs, duration of clinical signs for more than 3 months per year, and insufficient management with symptomatic therapy, due to side effects to the drugs used and/or poor owner compliance, justify in most cases allergy testing. These can be performed by IDT and ASIS. Both tests are not recommended as screening tests and should only be used to confirm the clinical diagnosis of canine AD. The results of these tests are also used to identify the offending allergen(s) in order to formulate an allergen-specific immunotherapy (ASIT).

·       Intradermal testing (IDT) 

The selection of test allergens should be made based on the prevalence of the allergens in a specific geographical region. Intradermal injections for IDT are most commonly performed on the lateral thorax, after the hair has been gently clipped and the injection sites marked (minimum 2 cm apart). Typically a volume of 0.05– 0.1 ml of each test concentration is injected intradermally and evaluated after 15–20 min. The reaction at each injection site will be compared between those of the positive (histamine phosphate) and negative (saline with phenol) controls. By convention, an allergen reaction is positive when the wheal formed is at least equal or greater than halfway between the negative and the positive control reaction. If the subjective evaluation is used, the positive control will assume a conventional grade of 4, whereas the negative control will be graded as 0. A reaction to an allergen is considered positive if it’s graded as 2 or greater.

·       Allergen specific IgE serology testing (ASIS)

These assays are used to detect specific IgE antibodies against a panel of allergens (e.g., pollen, mould, HDM and epidermal allergens) considered relevant for the patient.

Treatment

·       Allergen avoidance

If an allergen is known to trigger a flare, it is in the patient’s best interest to prevent further contact with such allergen. While this is the easiest to achieve in the case of flea, food and microbial allergens with flea control, diet restriction and antimicrobials, respectively, the prevention of contact with environmental allergens is difficult to impossible

·       Reactive anti-allergic therapy

Reactive therapy is the treatment of dogs with active skin lesions. It is best to continue the reactive therapy until a full and stable (e.g., two to four weeks) remission of signs before moving on to proactive therapy. For reactive therapy, several drugs have been shown to have a rapid (Glucocorticoids, Janus kinase inhibitors, Monoclonal antibodies) or slower effect (Calcineurin inhibitors).

1.      Glucocorticoids

Ø  Oral glucocorticoids (prednisolone) should be used at 0.5 mg/kg once- to twice- daily to induce remission of clinical signs of allergic pruritus in dogs.

Ø  After remission occurs, the dose of oral glucocorticoids should be tapered to the lowest dosage and frequency that maintains an absence of signs and minimises the risk of side effects over the long-term.

Ø  Topical glucocorticoids sprays, such as those containing triamcinolone or hydrocortisone aceponate, mometasone or methylprednisolone aceponate lotions can be used alone or in conjunction with oral glucocorticoids.

Ø  The major drawback to the use of systemic glucocorticoids in dogs is the potential adverse effects. Short-term use lead to polydipsia, polyphagia, panting, aggression and diarrhoea.

Ø  Prolonged use of glucocorticoids can lead to signs of iatrogenic hyperglucocorticism (muscle wastage, pot belly, hepatomegaly, fat redistribution, osteoporosis, calcinosis cutis, alopecia, poor wound healing, recurrent pyoderma, generalised demodicosis, comedones, pyelonephritis, cataracts, insulin resistant diabetes mellitus) and sudden withdrawal after prolonged therapy can lead to an Addisonian crisis (adrenal insufficiency).

 

2.      Janus kinase inhibitors (JAKinibs)

Ø  Oclacitinib administered at a dose of 0.4 to 0.6 mg/kg body weight, administered orally, twice daily for up to 14 days, and then administered once daily for maintenance therapy.

Ø  The drug is not approved for dogs under 12 months of age.

Ø  The most common adverse effects in the oclactinib is diarrhoea and vomiting.

Ø  The long-term administration of oclactinib administered once-daily appears to be relatively safe, whereas the long-term safety of other dosing regimens in not known.

3.      Monoclonal antibodies

Ø  Lokivetmab is a monoclonal antibody that specifically targets and neutralises canine IL-31, a key cytokine in the stimulation of pruritus in canine AD.

Ø  A single, subcutaneous injection at a minimum dose of 1 mg/kg typically provides a month of relief from pruritus. Repeat administration can be given monthly as needed in the individual patient.

Ø  Side effects are almost non-existent.

4.      Calcineurin inhibitors

Ø  Cyclosporin is a broad-spectrum oral immunosuppressant, which, at the dosage of 5 mg/kg/day until satisfactory control of clinical signs is achieved, which typically takes 4 to 6 weeks.

Ø  Thereafter, the dose required to maintain remission should be tapered by either decreasing the frequency from every day to every other day and then twice-weekly.

Ø  Adverse reactions in dogs receiving cyclosporine include gastrointestinal signs (vomiting, diarrhoea and reduced appetite) which are usually mild and transient. Gingival hyperplasia has been reported in dogs receiving cyclosporin.

Ø  Tacrolimus is a topical calcineurin inhibitor, which helps to reduce skin lesions.

·       Proactive therapy

Proactive (prophylactic) therapy is that of a dog whose signs are in remission to prevent their relapse.  Cyclosporin is one of the best drugs to use proactively in the long-term. Proactive topical glucocorticoid therapy (PTGT) (hydrocortisone aceponate) twice weekly, at the site of previously affected lesions to prevent their recurrence.

Ø  Allergen specific immunotherapy (ASIT) is the administration of increasing amounts of extracts of allergens to which the patient is hypersensitive to prevent or reduce flares of allergic diseases upon further contacts with the offending allergens. There is initially an induction phase with a slow increase in allergen dosing followed by a maintenance phase with less frequent injections of a higher concentration of extract. ASIT can be administered by several routes: subcutaneous, sublingual or intra-lymphatic. In dogs, ASIT is considered fairly safe and to, in average, result in a 60-70% of dogs having good-to-excellent results.

Ø  Antihistamines appear to have a limited benefit to control sings of AD, and they are probably more useful as antipruritic rather than to reduce skin lesions. Hydroxyzine (2 mg/kg twice daily) or cetirizine (1 to 2 mg/kg, once daily) are the antihistamines with proven pharmacodynamics effect in dogs.

·       Adjunctive therapy

Ø  Essential fatty acids (EFAs):

More recently, extensive research has brought to light the need to correct the skin barrier dysfunction seen in AD cases. It has been shown that in atopic dogs, there is an increase in the amount of transepidermal water loss (TEWL) in lesional and non-lesional skin. The oral intake of EFAs, especially those rich in omega-6 EFAs either as supplement or in enriched diets can help to restore the skin lipid barrier.

Ø  Shampoos

Non-irritant shampoos (e.g., Piroctone olamine) are an integral part of the management of AD.

Ø  Antimicrobial therapy

Antimicrobial therapy is needed in an atopic dog when a skin and/or ear infection with bacteria and/or yeast is diagnosed based on compatible clinical signs with or without supportive cytology or bacterial culture. The treatment of such infections usually consists of topical and/or systemic antimicrobials.

Conclusion

Canine AD is a chronic condition that can be difficult to manage and frustrating for owners and veterinarians alike. Prognosis for the long-term control of signs of AD is rather good. Treatment of this disease is clearly multifaceted and that interventions should be combined for a proven (or likely) optimal benefit. Furthermore, treatment should be tailored to each patient depending upon the stage of the disease, its severity and the distribution of lesions. Veterinarians should also remember to evaluate and then discuss with the pet owners the benefit of each recommended intervention, its side effects, its ease of administration, and its cost as a single or combined modality. Ultimately, the quality of life of both dogs and their owners, as well as the preferences of the latter, should be considered before a treatment plan is designed.

 

Case-study – Tsunami

Tsunami, a 2 year old, male, indie (non-descript) dog was presented with severe pruritus and lesions on face, limbs and trunk (Fig 3).  Skin scrapping examination was negative for mites. Wood’s lamp, cytology trichogram was negative for fungal infection.  An elimination diet trail (Hypoallergenic food) was conducted for 6 to 8 weeks with no result. Histopathological examination of skin biopsy (Fig 4) revealed hyperkeratosis, and mixed inflammatory infiltrate including mast cells in the sub-epidermal and perivascular compartment of the skin. There was response to initial glucocorticoid therapy and the dog was subsequently put on oral cyclosporin (5 mg/kg/day) for several weeks and then it was tapered down to twice weekly. The dog was given weekly bath with piroctone olamine shampoo. Topical tacrolimus (0.1%) ointment was used to control pruritus. Essential fatty acids (EFAs) were also used as adjunct therapy. Tsunami made excellent recovery in few weeks (Fig 5) after starting the cyclosporin therapy.

 

Bibliography

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2.     Jasmin, Pierre. “Atopic dermatitis.” Clinical Handbook on Canine Dermatology. 4^th ed., edited by Thierry Olivry, Virbac, 2020, pp. 119-132.

3.     Marsella, Rosanna, et al. "Current understanding of the pathophysiologic mechanisms of canine atopic dermatitis." Journal of the American Veterinary Medical Association 241.2 (2012): 194-207.

4.     Olivry, Thierry, et al. "Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA)." BMC veterinary research 11.1 (2015): 1-15.

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