Dermatologic adverse effect of subcutaneous furosemide administration in a cat.

Background: Furosemide is a mainstay of treatment in congestive heart failure (CHF) and is widely prescribed to dogs and cats by several formulations, including the subcutaneous one. In canine and human medicine, dermatologic adverse effects of subcutaneous furosemide (SF) have been documented; conversely, no prior case has been published describing skin reactions to this therapeutic protocol in cats. In this report, we describe, for the first time in feline medicine, a suspected dermatologic adverse effect after SF in a cat. Case Description: A 2-year-old domestic shorthair cat was presented for CHF associated with lung edema and pleural effusion. Echocardiography revealed asymmetric left ventricular myocardial thickening and severe left atrial dilation. The cat was hospitalized and initially treated with oxygen, intravenous furosemide, and clopidogrel. After discharge, the route of administration of furosemide was switched from intravenous to oral. Within the following 2 weeks, the cat experienced two relapses of lung edema despite the progressive increase of the furosemide dose, the addition of spironolactone and adherence to the therapeutic protocol by the owners. The dose of furosemide was further increased and its route of administration at home was switched from oral to parental. As the owner was not able to administrate intramuscular injections, SF was prescribed. This allowed the prevention of further episodes of lung edema. However, although the cat had never presented skin problems before, multiple well-defined circular, crusted ulcerative cutaneous lesions associated with alopecia developed at the sites of furosemide injections 2 weeks later. After ruling out several differential diagnoses for these lesions, a rare side effect of furosemide, not yet described in cats but already known in canine and human medicine, was strongly suspected as the possible cause. Therefore, the ongoing injectable formulation of furosemide was interrupted and substituted with an alternative brand, maintaining the same dose and route of administration. Thanks to this change, the dermal ulcerations disappeared within 1 month. Subsequently, the cat experienced neither further skin problems nor a recurrence of lung edema. Conclusion: Although SF is sometimes prescribed in small animal practice, it should be noticed that this may lead to dermatologic adverse reactions in the cat.

Cannabinoid receptors in the inflammatory cells of canine atopic dermatitis.

Background: Atopic dermatitis (AD) is one of the most common cutaneous inflammatory and pruritic diseases in dogs. Considering its multifactorial nature, AD can be a challenging disease to manage, and the therapeutic strategy must often be multimodal. In recent years, research has been moving toward the use of natural products which have beneficial effects on inflammation and itching, and no side effects. Cannabinoid receptors have been demonstrated to be expressed in healthy and diseased skin; therefore, one of the potential alternative therapeutic targets for investigating AD is the endocannabinoid system (ECS). Objective: To immunohistochemically investigate the expression of the cannabinoid receptor type 2 (CB2R), and the cannabinoid-related receptors G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) in mast cells (MCs), macrophages, dendritic cells (DCs), T cells, and neutrophils of the skin of dogs with AD. Animals: Samples of skin tissues were collected from eight dogs with AD (AD-dogs). Materials and methods: The immunofluorescent stained cryosections of the skins of 8 dogs with AD having antibodies against CB2R, GPR55, TRPV1, TRPA1 were semiquantitatively evaluated. The inflammatory cells were identified using antibodies against tryptase (mast cells), ionized calcium binding adaptor molecule 1 (IBA1) (macrophages/DCs), CD3 (T cells), and calprotectin (neutrophils). The proportions of MCs, macrophages/DCs, T cells, and neutrophils expressing CB2R, GPR55, TRPV1 and TRPA1 were evaluated. Results: The cells of the inflammatory infiltrate showed immunoreactivity (IR) for all or for some of the cannabinoid and cannabinoid-related receptors studied. In particular, MCs and macrophages/DCs showed CB2R-, GPR55-, TRPA1-, and TRPV1-IR; T cells showed CB2R-, GPR55- and TRPA1-IR, and neutrophils expressed GPR55-IR. Co-localization studies indicated that CB2R-IR was co-expressed with TRPV1-, TRPA1-, and GPR55-IR in different cellular elements of the dermis of the AD-dogs. Conclusions and clinical importance: Cannabinoid receptor 2, and cannabinoid-related receptors GPR55, TRPV1 and TRPA1 were widely expressed in the inflammatory infiltrate of the AD-dogs. Based on the present findings, the ECS could be considered to be a potential therapeutic target for dogs with AD, and may mitigate itch and inflammation.

Distribution of Cannabinoid Receptors in Keratinocytes of Healthy Dogs and Dogs With Atopic Dermatitis.

It is commonly accepted that some form of skin barrier dysfunction is present in canine atopic dermatitis (AD), one of the most common cutaneous pruritic inflammatory diseases of dogs. The impaired skin barrier function facilitates the penetration of allergens and subsequently stronger sensitization responses. The role of the endocannabinoid system (ECS) in the physiology and pathology of the skin is becoming increasingly established. It has been demonstrated that cannabinoid receptors are expressed in healthy and diseased skin and, based on current knowledge, it could be stated that cannabinoids are important mediators in the skin. The present study has been designed to immunohistochemically investigate the expression of the cannabinoid receptors type 1 (CB1R) and 2 (CB2R) and the cannabinoid-related receptors G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), peroxisome proliferator-activated receptors alpha (PPARα), and serotoninergic receptor 1a (5-HT1aR) in keratinocytes of healthy dogs and of dogs with AD. Samples of skin tissues were collected from 7 healthy controls (CTRL-dogs) and from 8 dogs with AD (AD-dogs). The tissue samples were processed using an immunofluorescence assay with commercially available antibodies, and the immunolabelling of the receptors studied was quantitatively evaluated. The keratinocytes of the CTRL- and the AD-dogs showed immunoreactivity for all the receptors investigated with a significant upregulation of CB2R, TRPA1, and 5-HT1aR in the epidermis of the AD-dogs. The presence of cannabinoid and cannabinoid-related receptors in healthy keratinocytes suggested the possible role of the ECS in canine epidermal homeostasis while their overexpression in the inflamed tissues of the AD-dogs suggested the involvement of the ECS in the pathogenesis of this disease, having a possible role in the related skin inflammation and itching. Based on the present findings, the ECS could be considered a potential therapeutic target for dogs with AD.