Female pug with swollen paws

Figure 1. (20X magnification, H&E stain) Skin with ulceration and widespread pyogranulomatous inflammation.

 Figure 2. (400X magnification, H&E stain) Skin, deep in the dermis, numerous refractile spherical organisms averaging 10um in diameter present within macrophages.
Figure 3. (400X magnification, mucicarmine stain) Skin with refractile spherical organisms averaging 10um in diameter.

SIGNALMENT
5-year-old, female spayed, Pug, canine.

SOURCE/HISTORY:Multiple pawpads were swollen for 3 months, treated with Mupirocin.

MICROSCOPIC DESCRIPTION:
Skin of the pads:  The epidermis is multifocally ulcerated. The superficial and deep dermis is severely inflamed with perivascular to diffuse macrophages. There are fewer plasma cells and a few neutrophils in the epithelium. A very large number of fungi are observed in the cytoplasm of macrophages. The organisms are about 10 microns in diameter and often have a central basophilic structure and a somewhat thick outline, sometimes resembling a shell, surrounded or surrounding a pale space. Histochemical stains show that the organisms are positive by PAS and GMS, but negative by mucicarmine and therefore not compatible with Cryptococcus. The organisms vary in size ranging from 3 to 30 microns and there are internal divisions that are compatible with Prototheca.

MICROSCOPIC INTERPRETATION:

Skin: Dermatitis, granulomatous, ulcerative, severe, locally extensive, chronic

COMMENTS:

Protothecosis is an infectious disease caused by saprophytic, achlorophyllous algae, achlorophylls, called Prototheca wickerhamii and Prototheca zopfii. The infection in humans is mainly cutaneous. Prototheca sp. is an opportunistic agent, invading contaminated wounds and mucous membranes. This alga is found in Europe, Asia and North America in soil, sewage, stagnant water, animal waste, tap water, water from streams and pools. It is a rare disease in dogs. It is more common in immunocompromised dogs. Collie dogs and females seem predisposed. Prototheca zopfii is often responsible for disseminated protothecosis. Only Prototheca wickerhamii has been isolated from cutaneous infections in dogs and cats, and Prototheca zopfii is nearly always isolated from disseminated infections in dogs.

Collies may be predisposed. In dogs, the disease is generalized, with multi-systemic involvement.  Multisystem involvement is characterized by the formation of granulomatous lesions, localized in various organs such as the kidneys, the brain, the spinal cord, the liver, skeletal muscles, myocardium and lymph nodes. Gastrointestinal sings can include hemorrhagic diarrhea due to chronic colitis and weight loss. Central nervous system signs can include depression, ataxia, vestibular involvement and paresis. Eye damage may be present (blindness, glaucoma, chorioretinitis, retinal detachment). More rarely, acute renal failure and osteomyelitis may be encountered.

In the cutaneous form, there is an inverse relationship between the number of infectious agents and cell infiltration, which suggests that the alga inhibits the local immune response or that only dead prototypes can trigger an inflammatory response. Dogs with cutaneous or mucocutaneous protothecosis usually do not have clinical signs of systemic involvement. Dermatologic lesions may include multiple papules and nodules, often over pressure points, or nodules and ulcers involving mucocutaneous junctions especially nostrils, scrotum and footpads. Depigmentation of the nasal planum may be striking. Lesions may become disseminated with spread to joints, lymph nodes, heart and lungs.

Clinical response to antimicrobial agents frequently fails to correlate with in vitro susceptibility test results. Amphotericin B, sodium iodide, amphotericin B and tetracycline or itraconazole, ketoconazole, aminoglycosides and tetracyclines have been proposed, generally with poor response; therapy is usually prolonged (2-4 months) and should be continued for 3-4 weeks beyond the clinical curative. In one dog, skin lesions continued to recur each time ketoconazole administration was stopped, even after treatment periods of ten months. Topical clotrimazole may be a useful adjuvant for the treatment of skin lesions caused by P. wickerhamii. The prognosis is poor with generalized signs and when the skin lesions are no longer surgically resecaible.

Reference: Miller, Griffin, Campbell 2013. Muller and Kirk’s small animal dermatology seventh edition, page 272, Elsevier.

PATHOLOGIST:

Melissa Behr, DVM, Diplomate ACVP

Direct line: 207-556-6699

1-800-551-0998, x66699

melissa-behr@idexx.com

Prototheca est une algue achlorophylle saprophyte omniprésente dans le sol et dans de nombreux autres endroits. Ce micro-organisme provoque des infections opportunistes, et une maladie disséminée est souvent associée à un dysfonctionnement de l’immunité de l’hôte. Seul Prototheca wickerhamii est isolé dans les infections cutanées chez les chiens et les chats, alors que Prototheca zopfii est presque toujours isolé dans les infections disséminées chez les chiens. Les lésions contenant un grand nombre d’organismes ont généralement peu d’inflammation environnante. Les infiltrats de cellules mononucléaires augmentent après le début du traitement et le nombre d’organismes dans les tissus diminue. Ces résultats suggèrent soit que Prototheca inhibe la migration leucocytaire, soit que les micro-organismes morts induisent une réponse immunitaire.

Les chiens atteints de protothécose cutanée ou mucocutanée ne présentent généralement pas de signes cliniques d’atteinte systémique. Les lésions dermatologiques peuvent inclure de multiples papules et nodules, souvent au-dessus des points de pression, ou des nodules et des ulcères impliquant des jonctions mucocutanées, en particulier les narines, le scrotum et les coussinets. Une dépigmentation marquée du plan nasal peut survenir. Les lésions peuvent se disséminer et se propager aux articulations, aux noeuds lymphatiques, au cœur et aux poumons.

Dans le cas de Prototheca, la réponse clinique aux agents antimicrobiens ne corrèle souvent pas avec les résultats des tests de sensibilité in vitro. L’amphotéricine B, l’iodure de sodium, l’amphotéricine B avec la tétracycline ou l’itraconazole, le kétoconazole, les aminosides et les tétracyclines ont été proposés, généralement avec une réponse médiocre; le traitement est généralement prolongé (2 à 4 mois) et doit être poursuivi pendant 3 à 4 semaines après la résolution de la maladie clinique. Un rapport de cas a même décrit une infection chez un chien où les lésions cutanées récidivaient à chaque fois que l’administration de kétoconazole était arrêtée, même après des périodes de traitement de dix mois. Le clotrimazole topique peut être un adjuvant utile pour le traitement des lésions cutanées causées par P. wickerhamii.

Référence: Miller, Griffin, Campbell 2013. Muller and Kirk’s small animal dermatology septième édition, page 272, Elsevier.

Prototheca are ubiquitous saprophytic achlorophyllous algae found in soil and many other locations.  The organism causes opportunistic infections, and disseminated disease is often associated with dysfunction of host immunity. Only Prototheca wickerhamii is isolated from cutaneous infections in dogs and cats, and Prototheca zopfii is nearly always isolated from disseminated infections in dogs. Lesions with large numbers of organisms typically have little surrounding inflammation, and mononuclear cell infiltrates increase after therapy is started, and numbers of organisms in tissues decrease. These findings suggest either that protothecal organisms inhibit migration, or that dead organisms induce an immune response.

Dogs with cutaneous or mucocutaneous protothecosis usually do not have clinical signs of systemic involvement. Dermatologic lesions may include multiple papules and nodules, often over pressure points, or nodules and ulcers involving mucocutaneous junctions especially nostrils, scrotum and footpads. Depigmentation of the nasal planum may be striking. Lesions may become disseminated with spread to joints, lymph nodes, heart and lungs.

Clinical response to antimicrobial agents frequently fails to correlate with in vitro susceptibility test results. Amphotericin B, sodium iodide, amphotericin B and tetracycline or itraconazole, ketoconazole, aminoglycosides and tetracytlines have been proposed, generally with poor response; therapy is usually prolonged (2-4 months) and should be continued for 3-4 weeks beyond the clinical curative. In one dog, skin lesions continued to recur each time ketoconazole administration was stopped, even after treatment periods of ten months. Topical clotrimazole may be a useful adjuvant for the treatment of skin lesions caused by P. wickerhamii.

Reference: Miller, Griffin, Campbell 2013. Muller and Kirk’s small animal dermatology seventh edition, page 272, Elsevier.

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