Juvenile cellulitis (juvenile sterile granulomatous dermatitis and lymphadenitis) in a 9-week-old puppy treated with prednisolone-cyclosporine combination therapy

Juvenile sterile granulomatous dermatitis and lymphadenitis (also called juvenile cellulitis or puppy strangles) is an uncommon, fulminant granulomatous and pustular disease of puppies, typically from 3 wk to 4 mo of age (1–3). Older age onset may occur; thus, older puppies and adult dogs exhibiting typical lesions and progression associated with juvenile cellulitis should be evaluated for this disease (4–6). Facial skin, pinnae, and submandibular lymph nodes are usually affected and there may be concurrent lesions on the trunk as well as preputial or perianal areas. Initial lesions that are typically reported include acute facial edema and striking submandibular lymphadenopathy. Papules, pustules, vesicles, cellulitis, and alopecia develop, lesions may fistulate, draining serous to purulent exudate, with crusting. Ear pinnae may be swollen and exudative (1,3). Affected skin may be painful but is not pruritic, although secondary skin or ear infection may cause pruritus (1). Systemic signs of illness such as lethargy, depression, anorexia, and fever may be present.

Case description

A 9-week, 3-day-old intact male Cavalier King Charles spaniel was presented with a 10-day history of lethargy and inappetence, followed by progressive development of granulomatous, abscess-like lesions, fistulation, purulent exudation on neck and face, as well as facial perioral papules and pustules. Perioccular edema had been noted. Moderate otic and facial pruritus was present. A complete blood (cell) count (CBC) performed by the referring veterinarian had revealed leukocytosis, neutrophilia, lymphocytosis, and monocytosis with mild anemia. Serum chemistry test results were unremarkable. Fine-needle aspirate from subcutaneous nodules had revealed pyogranulomatous, sterile inflammation. Short course prednisolone acetate therapy 2.0 mg/kg BW, PO, q24h for 5 d was considered ineffective. Polydipsia and polyuria were noted with corticosteroid use. Amoxicillin-clavulanate potassium 25 mg/kg BW, PO, q12h for 7 d, Cothivet spray (Vétoquinol; Hydrocotyle Tincture Topical Spray 89.5% V/V), q6–8h topically, and frequent warm compresses were used at lesional sites. Otic Aurizon therapy had been discontinued previously due to concern for a possible cutaneous adverse drug reaction (CADR), due to rapidly progressing cutaneous signs.

The initial symptom of juvenile cellulitis exhibited by the puppy was likely otitis externa, prior to adoption at 8 wk of age. At adoption, otitis was reported to pet owner by the breeder, who had initiated Aurizon ear drops (Vétoquinol; marbofloxacin, clotrimazole, and dexamethasone acetate) topically. The exact timing of onset of symptoms, therefore, was unclear.

On initial physical assessment (Day 0), superficial crusts, patchy alopecia, papules, pustules, nodules and abscessation, with draining tracts were noted on face, neck, and dorsal chest (Figure 1). Localized perianal crusting and hyperkeratosis of multiple footpads were noted. Concave pinnae exhibited scaling, dry crusts, hair matting, and occasional erosions. Otoscopic examination revealed significant ceruminous gland hyperplasia, suppurative otic discharge, with stenosis along ear canals bilaterally (Figure 2). Moderately enlarged, non-sensitive submandibular lymph nodes were palpable bilaterally. Other peripheral lymph nodes and the rest of the physical examination were unremarkable; no fever or pain were evident. Cutaneous cytology was largely consistent with previous results from fine-needle aspiration, indicating sterile, pyogranulomatous inflammation. Cytological evidence of bilateral suppurative bacterial otitis externa as well as localized superficial chin and perianal pyoderma was present. Deep skin scrapings and bacterial culture testing from the right lateral neck abscess helped rule out demodicosis and deep bacterial skin infection, respectively. Juvenile cellulitis was considered likely and biopsy testing for confirmation was recommended but the pet owners opted for a conservative, empirical medical treatment approach. Treatment advised included continued prednisolone acetate 2.0 mg/kg BW, PO, q24h, with the addition of cyclosporine (Atopica; Elanco), 4 mg/kg BW, PO, q24h, to help minimize the need for steroid use. Topical antibacterial therapy included use of chlorhexidine gluconate 4% medicated wipes (DermaChlor 4 wipes; Dechra) q24h for chin and perianal skin, and otic therapy using compounded TrizEDTA aqueous solution (Dechra) with amikacin and dexamethasone added. Discontinuation of Clavamox and Cothivet therapy was advised, and a follow-up examination was planned for 2 wk later.

Figure 1.

Juvenile cellulitis associated facial and lateral neck lesions on initial presentation in a 9-week-old puppy, including superficial crusts, alopecia, nodules, abscessation, and draining tracts.

Figure 2.

Suppurative bacterial otitis externa in a puppy affected by canine juvenile cellulitis.

At follow-up on Day 15, the puppy had significantly improved activity and appetite, was gaining weight, dorsal chest and neck lesions had resolved, and there were significant facial skin and bilateral otic improvements. Cytologically persistent mild right bacterial otitis was noted along with resolved left bacterial otitis, and chin and perianal pyoderma. Submandibular lymph nodes were normal on palpation. The CBC-chemistry-urinalysis revealed persistence of leukocytosis and neutrophilia, with normalized red cell, lymphocyte, and monocyte counts. Mild elevations in alkaline phosphatase and creatinine kinase were noted. Prednisolone (1.87 mg/kg BW, q24h, PO) and cyclosporine (6.25 mg/kg BW, q24h, PO) were continued. Triz EDTA compounded otic therapy (amikacin and dexamethasone added) was extended for another 10 d, for the right ear.

At virtual follow-up on Day 31, continued improvements were reported along with recent onset of substantial polydipsia and polyuria. Prednisolone dosage was lowered to 0.96 mg/kg BW, q24h, PO for 5 d, followed by 0.96 mg/kg BW, q48h, PO. At Day 31, the puppy exhibited normal cutaneous and otic health (including otic cytology and otoscopy) with no cutaneous lesions observed in the previous 2 wk (Figure 3). Cyclosporine was discontinued and prednisolone discontinuation with short taper was advised (0.84 mg/kg BW, q72h, PO for 15 d). At the Day 119 update, the puppy was reported to be in good health with no signs of relapse.

Figure 3.

Resolved facial and lateral neck skin lesions with lateral neck hair regrowing, at Day 48 examination, on prednisolone-cyclosporine therapy.

Discussion

The exact cause of juvenile cellulitis is unknown. As noted in this case, immune dysfunction is supported by dramatic response and resolution of sterile granulomatous and pustular lesions with immunosuppressive therapy (1,3,7). Sole corticosteroid therapy is generally pursued using immunosuppressive doses; cyclosporine-prednisone combination therapy is also effective and can be considered to help minimize the adverse effects of corticosteroid administration or in patients inadequately responsive to sole corticosteroid therapy (3,6,7). In this case, oral cyclosporine was added as symptoms of juvenile cellulitis were progressing despite recent sole prednisolone therapy and adverse effects (polydipsia-polyuria) were concerning.

Frequent client communication and patient examinations in juvenile cellulitis patients are recommended for assessment of adverse effects related to immunosuppressive drug therapy, treatment adjustment in growing puppies, and for monitoring secondary infection development, treatment, and/or resolution. Immunosuppressive therapy is tapered off after lesion and symptom resolution. Relapses are uncommon after resolution of signs, although relapses may be more common in adult-onset disease (6).

When there is cytologic or culture-based evidence of secondary bacterial infection, systemic antibiotic therapy has been historically recommended (1). However, with increased drug-resistant canine skin infections in the past decade, empirical antibiotic therapy is discouraged. Clinical lesions of juvenile cellulitis are usually severe enough to give the false impression of bacterial pyoderma involvement, despite it being a sterile disease process. Therefore, cytological evidence of bacterial pyoderma should be sought before deciding on antimicrobial therapy options. Localized topical chlorhexidine therapy was used in this case, as superficial bacterial pyoderma responds well to frequent topical antimicrobial therapy (8,9). In the absence of deep bacterial infection, systemic antibiotic therapy was not required, although prior to Day 0 assessment, a short course oral amoxicillin-clavulanate potassium therapy may have been effective for secondary deep bacterial infection.

Purulent otitis is a reported finding in juvenile cellulitis (1). In this case, otitis externa was likely the initial sign of juvenile cellulitis, noted by the breeder. Despite the patient being apparently comfortable and non-pruritic at ears after ear treatment, significant ear canal changes and bacterial otitis were detected on detailed examination. These findings emphasized the need to perform a thorough otic examination for all dogs suspected to be affected with juvenile cellulitis (and with dermatological disease in general), including otoscopy and otic cytology testing. Furthermore, as immunosuppressive therapy is the primary treatment for juvenile cellulitis, close monitoring of ear health is indicated throughout juvenile cellulitis treatment, as a secondary ear infection may develop during therapy. Similarly, development of bacterial pyoderma, Malassezia dermatitis, and/or iatrogenic demodicosis should be monitored during therapy, and diagnostic cutaneous cytology and deep skin scrapings performed if novel or non-responding skin lesions are noted.

Differential diagnoses of juvenile cellulitis may include angioedema, dermatophytosis (when significant scale, crusts, and alopecia are present), demodicosis, adverse cutaneous drug reaction, sterile nodular panniculitis, infectious panniculitis, and canine distemper (1,3). Cutaneous adverse drug reaction (CADR) was considered the primary differential diagnosis in this case, due to rapid progression of cutaneous and systemic clinical symptoms after addition of drug therapy, including Aurizon topical otic therapy initially and subsequently oral amoxicillin-clavulanate potassium therapy. Cutaneous adverse drug reaction can often be a differential diagnosis in juvenile cellulitis patients, due to rapid progression of clinical signs, despite addition of early, empirical treatments. In this case, CADR could not eventually be ruled out or confirmed through re-exposure of suspected offending treatments, from patient safety as well as antimicrobial stewardship standpoints. Concomitant CADR and juvenile cellulitis cannot be ruled out, as co-existing diagnoses are possible. Development of pemphigus foliaceus-like drug reaction has been reported in a patient being treated for juvenile cellulitis (10). Deep infection such as an abscessed wound due to bite or other trauma was considered, although there was no historical evidence of a traumatic event. Negative bacterial culture testing of deep lesional purulent discharge followed by excellent responsive to immunosuppressive therapy helped in ruling out this possibility.

Histopathology testing was not pursued in this case, in part due to the classical presentation of juvenile cellulitis, fine-needle aspirate, and cutaneous cytological findings, and preference for empirical therapy due to financial considerations. When pursued, biopsy sampling of early lesions is preferred for definitive diagnosis, including intact pustules, vesicles, or nodules (2). Histopathology findings include normal to acanthotic epidermis, with or without ulcerated lesions. The dermis is most often characterized by multiple discrete or confluent granulomas and pyogranulomas, comprising nodular clusters of large epithelioid macrophages and neutrophils. Pyogranulomas are often oriented around follicles, typically do not invade follicular walls, and can extend to the panniculus and subcutis (2).