Idiopathic Recurrent Pyoderma: Causes, Diagnosis, & Management

Sponsored by Delmont Laboratories

Abridged from previous conference proceedings by Dr. Douglas J. DeBoer.

Staphylococcal bacteria are part of a normal skin flora and are always present; infection occurs with pathology of the skin or its defense systems.

A comprehensive and appropriate diagnostic investigation is the first step to address recurrent staphylococcal infections and define their cause. Ectoparasites and allergic disease are common causes of recurrent pyoderma in young dogs; underlying systemic disease (eg, hypothyroidism) can result in recurrent infection in older dogs. 

Even after thorough testing, some infections that respond completely to antibiotic treatment will recur soon after cessation of treatment. For these “idiopathic recurrent pyoderma patients,” there are options to help to prevent or manage recurrence.

Bacterial & Host Factors in Pathogenesis

Adherence of bacterium to cell or tissue initiates infection, and staphylococci adhere better to canine skin cells than feline skin cells.¹ 

Defensins are bactericidal peptides secreted by the epidermis as part of its defense system. In humans, and potentially in dogs,² atopic dermatitis patients sometimes have lower production of defensins than nonallergic individuals, suggesting predisposition to recurrent infection.<sup2 sup> 

Studies have attempted to analyze specific bacterial qualities (eg, certain species or strains of Staphylococcus) that make it particularly virulent or prone to cause recurrent infection; however, none have thus far been found, suggesting host factors may play a primary role. Complicating matters is the increase in reports of multidrug-resistant staphylococcal strains, particularly the methicillin-resistant staphylococci (MRS).³

Special Considerations

Several forms of pyoderma have additional factors that contribute to pathogenesis, further complicating treatment:

• In deep pyoderma secondary to generalized demodicosis, treatment of the staphylococcal infection, without treatment of mites, will be ineffective. 

• German shepherd dog pyoderma and cellulitis is an especially treatment-resistant form of deep pyoderma with evidence of a genetically determined cellular immunodeficiency.<sup4 sup> 

• Interdigital pyoderma (ie, interdigital cysts, interdigital inflammatory disease) is a familiar and frustrating condition. In addition to the staphylococcal infection, ruptured follicular cysts can be an initiating factor,⁵ and deep infection between the digits entraps hair fragments within developing scar tissue, leading to a draining, purulent, foreign-body reaction to the hair shafts. Interdigital pyoderma is much more than just a deep staphylococcal infection and can subsequently be difficult to treat.

Assessing Patients with Recurrent Staphylococcal Pyoderma

Early and routine procedures such as careful history taking; physical examination; and skin scrapings, trichograms, and/or empirical parasite control are essential to address any common cause of recurrence. 

Typical clinical signs of superficial pyoderma include papules, pustules, and epidermal collarettes often (but not always) with pruritus. Skin cytology should be pursued to confirm presence of neutrophils and cocci (ie, the expected result) and the absence of rod bacteria, which would indicate non-staphylococcal disease or complication of the staphylococcal infection with other opportunists.

Following this, the patient’s response to antimicrobial treatment is a valuable clue to underlying factors and will aid greatly in planning logical diagnostic evaluation to uncover the predisposing factors for each patient. 

The goal, at some point during the diagnostic period, is to assess the dog’s response to antimicrobial treatment alone, without interference from antipruritic or anti-inflammatory drugs. In other words, if the dog were to be treated with antimicrobials alone, for perhaps 3-4 weeks, what would the response be, and what clinical signs would remain? The main underlying causes of canine recurrent pyoderma may be divided into 4 groups, partly based on response to antimicrobial treatment (see Figure 1).

The 4 groups of underlying causes can then be examined more carefully, depending on response.

1. If the response to antimicrobials alone is a complete clearing of lesions, yet with substantial remaining pruritus, allergic causes should be strongly considered as underlying causes, particularly in young dogs.

2. If the response is a partial clearing of the lesions, but the skin is not totally normal and pruritus remains, underlying factors to consider include inadequate treatment, parasitism, longstanding environmental and/or food allergy with chronic skin changes, primary seborrhea, and dermatophytosis. Diagnostic steps in this case might be selected from the following list: repeated skin scrapings, empirical treatment for scabies mites, a dietary restriction-provocation trial, fungal culture, and/or skin biopsy. 

3. If there is little or no clinical response to antibiotic treatment, factors such as antibiotic resistance or poor client compliance should be considered. It is also possible that the diagnosis is wrong—non-pyoderma pustular diseases such as pemphigus foliaceus should be considered. Bacterial culture and susceptibility testing, fungal culture, and skin biopsy should be most strongly considered with this response pattern.

4. If the response is a complete clearing of both lesions and pruritus, the main underlying factors to consider include systemic disease (especially in an older dog); very early allergic disease (in a younger dog); and idiopathic recurrent superficial pyoderma. In this event, diagnostic evaluation may include evaluation for systemic disease with blood and urine analyses, or possibly further close monitoring for development of more typical signs of allergic disease. Failing to find a specific cause, the diagnosis of “idiopathic recurrent pyoderma” can be made; several treatment options are available for attempting long-term control and prevention of recurrence.

One consideration with this approach is the temptation to use concurrent antipruritic or anti-inflammatory treatment with the antimicrobial. Because pruritus is often the client’s chief complaint, a failure to address it may not be considered ideal. Here, a strong argument could be made to avoid concurrent corticosteroid treatment. Although glucocorticoids may relieve some of the pruritus, they are also anti-inflammatory and will suppress visual evidence of infection (ie, papules and pustules). This is hazardous, because it creates the appearance that the infection is resolved, when it is not—and this frequently leads the owner to prematurely stop the antimicrobial treatment. The result: as soon as the steroid is stopped, the infection makes a dramatic reappearance—as does an unhappy owner!

Although there are no studies to guide using newer antipruritic treatments (eg, oclacitinib or lokivetmab) in these cases, because these treatments are more antipruritic than broadly anti-inflammatory, it appears they may suppress pruritus, but not visible lesions. This may be a more favorable situation than use of corticosteroids; however, it still will not enable the clinician to judge the effects of the antimicrobial treatment alone, which is a valuable piece of clinical evidence.

The author’s preferred approach to this is to begin antimicrobial treatment alone, without any antipruritic or anti-inflammatory medications, while educating the owner regarding the reason behind this approach. An example of this communication might be:

Mrs. Jones, Fluffy has a bacterial infection. I think that may be what is causing the itch, so we’d like to start her on antimicrobial treatment. Now we could also give her something like cortisone to cover up the itch, but I’d rather not do that right away. Let’s just see if the antimicrobial alone relieves the itch. But if she is not improving over the next few days, please let me know, and we’ll have you pick up an additional medication to help the itch directly.

Anecdotally, clients often respond positively to this approach, appreciating the veterinarian is hesitant about the use of “steroids.” If the pruritus does not start to resolve over a few days, adding a brief course of oclacitinib may provide rapid and temporary relief while the antimicrobial continues to work. Because the effects of oclacitinib wear off rapidly, stopping it as soon as the infection has cleared can allow assessment of the true effect of the antimicrobial treatment.

Methicillin Resistant Staphylococci (MRS): An Added Complication

Recently, reports of multidrug-resistant staphylococcal strains and MRS in canine pyoderma have been increasing.³ Skin cultures performed at dermatology practices in some areas of the United States have shown more than half to be MRS. These strains include the methicillin-resistant Staphylococcus pseudintermedius species (MRSP) and occasionally S schleiferi. Methicillin-resistant S aureus species (MRSA) preferentially colonize and infect human beings, and thus infections in dogs are fortunately much less common. Of note, clinicians should use correct terminology when discussing these infections with clients; incorrectly referring to a canine MRSP infection as “MRSA” may be alarming to the owner, particularly if they perform online searches after their appointment.

A word on primary treatment of staphylococcal skin infections is in order, because recommendations have changed substantially in the past few years. The major thrust of newer recommendations is to reduce, as much as possible, use of systemic antibiotics when treating staphylococcal skin infections.⁶ Reduced antibiotic use will translate to limiting development of resistance in these bacteria over time. For most superficial staphylococcal pyoderma infections in dogs, the current treatment of choice is not antibiotics, but rather topical medications (Figure 2). There are situations in which antibiotics are still appropriate and necessary—for example in any dog with deep pyoderma, or perhaps in especially severe or widespread cases of superficial pyoderma. Regarding antibiotic choice, if susceptibility testing indicates the presence of MRS, the isolate will be clinically resistant to all penicillins and cephalosporins. Strains of MRS are typically multi-drug resistant, and it is impossible to empirically guess at the best antibiotic choice. Culture and susceptibility testing is always indicated at this point. Continuing treatment with an antibiotic to which the strain is not sensitive, based on empirical choice, only prolongs recovery and leads to worsening of the infection. Empirical “antibiotic hopping” is hazardous, as with each cycle of treatment, multiple drug resistance becomes more likely.

From a practical standpoint, if a dog with staphylococcal pyoderma has shown limited or no response to treatment with a beta-lactam antibiotic (cephalosporin or penicillin), culture and susceptibility testing should be considered mandatory. Although most veterinary strains of MRS are still susceptible to commonly used antibiotics (eg, trimethoprim-sulfamethoxazole, clindamycin, fluoroquinolones), susceptibility testing is still necessary in order to determine which of these might be appropriate in an individual patient.

In cases in which an MRS organism has been identified by the laboratory, particularly if the organism is very resistant, the public health and sanitation implications must be considered. MRSP is not typically transmissible to people, but travel to and colonization of other dogs in the waiting, exam, or kennel areas is possible. In this situation, an MRSP-infected patient need not undergo full isolation procedures (eg, personnel wearing mask and gown); however, the patient should be isolated as much as possible. Traffic from this patient to other dogs in the clinic, especially the surgery and critical care areas, should be eliminated. If the organism is identified as a methicillin-resistant, human-origin S aureus (MRSA), the owner should be notified and advised to consult with his or her healthcare provider. In this case, the patient must be considered a potential human health hazard until lesions have completely resolved; gloves and disposable gowns should be worn during examination or treatment of the patient in your facility. Without exercising appropriate precautions, MRSA could colonize the owner, you, your staff, or others. It is important to understand that mere colonization with MRSA is not inherently dangerous; 3% to 5% of humans are colonized at any given time, and colonization is dynamic and transient. The potential danger arises if the MRSA-colonized person becomes injured or immunosuppressed. The emergence of MRS also increases the importance of thorough disinfection of any examination area between patients.

Reducing Antimicrobial Use and Preventing Infection: The Role of Topical Antimicrobials

Topical antimicrobials are the first line of defense when treating superficial pyoderma, or attempting to prevent its recurrence. Products containing 2% to 4% chlorhexidine appear especially helpful.^6,7 For primary treatment, they should be applied once daily at home, for 3-6 weeks until the infection is completely healed. A combination shampoo with both chlorhexidine and miconazole can be even more beneficial. The miconazole helps to eliminate any concurrent yeast infection, but also has antimicrobial properties that are synergistic with chlorhexidine, even in MRS strains.⁸ Other ingredients (eg, benzoyl peroxide) are also effective but tend to be drying and irritating with prolonged use. Chlorine-containing “bleach” shampoo products are commercially available and may be a good choice for dogs that seem to be irritated by other products. Preliminary evidence suggests that products containing microparticulate silver in addition to chlorhexidine may have extended action.⁹

Daily topical application quickly becomes a compliance problem for most owners; daily baths are generally impractical. Non-shampoo topicals formulated to remain on the skin are often easier for owners to apply and may have a longer duration of action on the skin than do shampoos. Creams, ointments, or wipes may be adequate when treating localized lesions. When broader areas are affected, spray-on products, mousse formulations, or “leave-on” conditioner products are recommended. A frequently-recommended schedule is shampooing once weekly, plus spray or mousse application once daily on the non-shampoo days.

If the goal is not primary treatment, but rather preventing relapse of recurrent pyoderma, daily application is not necessary. Begin with twice-weekly application. In some patients, these can be tapered down to every 1-2 weeks if shown to be effective. The goal is to limit prolonged or repeated antibiotic treatment as much as possible in order to minimize the potential for development of antibiotic resistance.

Another related piece of advice that is especially relevant in today’s situation: in years past, continuous antibiotic treatment via pulse therapy was sometimes recommended as a last-resort treatment for recurrent pyoderma. However, with emerging resistance, this treatment technique should be completely avoided. Such practice is virtually guaranteed to rapidly result in colonization by a resistant strain, a phenomenon that is growing worldwide.

Immunomodulatory Bacterins

In some cases of canine idiopathic recurrent superficial pyoderma, and in cases of recurrent pyoderma associated with atopic dermatitis, immunomodulatory therapy can be very effective.^10,11 Its use for recurrent deep pyoderma is less well studied, though there are anecdotal reports of effectiveness in some dogs.¹² Staphylococcal bacterin products appear particularly useful. These “staph vaccines” were long used in the dairy industry to control staphylococcal mastitis. Currently, the only commercially licensed product for canine use is Staphage Lysate (SPL)® (Delmont Laboratories). SPL® has a variety of immunomodulatory actions; while it is uncertain which of these is most important in dogs, gene-expression microarray studies suggest it may exert its effects via up-regulation of interferon-gamma production.¹³

The main benefit of staphylococcal bacterin therapy is in preventing recurrence, rather than primary treatment; primary treatment is still the job of the antimicrobial. While bacterin therapy must generally be continued long-term to prevent recurrence, its use negates the need for prolonged or repeated antibiotic courses in many pets.

Treatment Protocol

(See Figure 3.)

SPL is administered at 0.5 mL subcutaneously, twice weekly. The product is easy for most owners to administer at home, with small-needle 1-mL syringes. During the first 3-6 weeks of injections, antimicrobial topical or systemic treatment is used concurrently. After 3-6 weeks, the infection will be resolved; then, the antimicrobials are stopped and the injections continued for a total trial period of 10 or more weeks. Success is manifested as failure to relapse (the hoped-for effect), or much milder, self-limiting relapse, or much less frequent relapse compared with before use of the SPL. Injection frequency can usually then be reduced to once-weekly or sometimes once every 2 weeks. If effective, the author recommends a full year of treatment; after this, injection frequency can be reduced even further. In a few patients, injections eventually can be stopped completely, and the beneficial effect will continue long-term.

The emergence of MRS in the veterinary world emphasizes the need to use antibiotics wisely and judiciously. When possible, efforts should be made to use alternative, nonantibiotic treatments when faced with recurrent infections. Topical treatments and staphylococcal bacterin treatment are excellent options for accomplishing this goal.