THERAPEUTIC APPROACH TO AUTOIMMUNE SKIN DISEASES IN VETERINARY DERMATOLOGY Anthony A. Yu DVM, MS, ACVD Guelph Veterinary Specialty Hospital yuvetpc@gmail.com Causes of alopecia Folliculitis Dermatophytosis Immune-mediated Pyoderma Alopecia areata Demodicosis DLE/SLE Endocrine Hypothyroidism Hyperadrenocorticism Sertoli cell tumour Ovarian cyst/tumour Alopecia X Nutritional Deficiency - protein, EFA, Vit A Congenital Pemphigus complex Sebaceous adenitis Neoplasia Epitheliotropic Lymphoma Mast cell tumor Psychogenic Acral lick dermatitis Feline psychogenic alopecia Traumatic Allergic Dermatitis Ectodermal defect Traction alopecia Feline alopecia universalis/ hypotrichosis Thermal burn Hereditary Colour dilution alopecia Follicular dysplasias Dermatomyositis Miscellaneous Canine recurrent flank alopecia Telogen defluxion Anagen defluxion They all look alike NOT!! Terra Cotta Museum Pit 1 Xian 2005 5 25 1
Alopecias Are Not Alike Loss of telogenized hairs in frictional areas dorsal muzzle, tail, back HypoT4, Cushing s, sex hormone, Alopecia X Post-clipping alopecia telogen phase when hair is shaved vasoconstriction dt cold temp at shaved area Hair growth at sites of trauma Alopecia X dt PDGF Hair loss affecting one colour follicular dysplasia genetic Hair loss affecting abnormal colours Color Dilution Alopecia Treatment of Alopecia.Questions?? Knit a Sweater!!! Cushing s unusual clinical findings Loss of muscle mass Split ends Coat color change Collagen breakdown n Spay incision n Poor healing wounds Anterior cruciate rupture Reproduction failure n ê FSH failure to cycle n ê LH testicular atrophy Secondary hypothyroidism n ê TSH reversible hypothyroidism 2
Cushing s Syndrome Pituitary Tumor Lysodren 25-50mg/kg 1-3X/week Trilostane 1-2.5 mg/kg BID Retinoid therapy Adrenal Tumor Hi Dose Lysodren Trilostane Surgery Feline Cushing s Syndrome Trilostane Adjust thyroid dose Treatment Trilostane n competitive inhibitor of 3β HSD n competitive inhibitor of 11β HSD?? 2-5mg/kg q24h OR 1-2.5 mg/kg BID ACTH 4-6h post Trilostane 10d, 4wks, 3mos, 6-12 mos goal post-acth = 50-150 nmol/l 4-6h post Trilostane post-acth>250 nmol/l double the dose post-acth<20 nmol/l, d/c 2d, next lower dose SE: cost, lethargy, anorexia, V/D, adrenocortical necrosis or hyperplasia, hypoadrenocorticism Unsusual signs of Hypothyroidism Muscle atrophy Facial nerve paralysis Acral lick granuloma Ceruminous otitis externa ACL rupture Laryngeal paralysis/voice Megaesophagus Cardiomyopathy Peripinnal hyperkeratosis 3
Peripinnal hyperkeratosis Hypothyroidism Levothyroxine 0.02 mg/kg BID S.E. = anxiety, panting, PU/PD Adjust dose if concurrent illness or cardiac compromise 6 hour post-pill Total T4 Expected responses 7 days behavior 4-6 wks hair/scale 3 months - normal Girlfriend 3 months post-thyroid 4
Before and post-supplementation Alopecia X Adrenal sex hormone imbalance Adrenal hyperplasia-like syndrome Growth hormone-responsive alopecia Castration-responsive alopecia Alopecia of plush-coated breeds Pomeranian, Chow Poodle, sled breeds M/F; neutered or intact Malamute or Husky Coat Funk Biopsy-responsive alopecia Pseudo-Cushing s Syndrome 5
Alopecia X : The presentation Gradual loss of hair of ventral neck, caudal thighs, trunk Hyperpigmentation Alopecia X : possible pathogenesis Pathogenesis unknown Abnormality in adrenal steroid production Altered adrenal or gonadal sex hormones Possibly a combination of cortisol and sex hormones causing arrest of hair cycle Partial 21-hydroxylase deficiency Different breeds = different pathomechanisms?? We are just as confused as Donald Rumsfeld Adrenal Steroidogenesis Cholesterol 3B-HSD Progesterone 17-OHP DHEAS 21-OH 3B-HSD 3B-HSD Aldosterone 21-OH Androstenedione Cortisol Testosterone Estrogen 6
Is treatment VooDoo? only partly First, spay / neuter if intact Anticipated response in 3-6 months Next try: Melatonin (30-40% success) 1 mg/kg/day divided TID Knit sweaters OR Lysodren Trilostane Cyclosporine?? Lupron Growth Hormone Methyltestosterone Allow 3-6 months before moving to next option Low dose Lysodren 15-25mg/kg daily 7-14 days, then weekly Watch Coumpounding RX One month after starting Lysodren Trilostane Orally active steroid analogue Competitive inhibitor of the 3 B- hydroxysteroid dehydrogenase enzyme system Blocks production of several adrenal steroids Possible side effects Hypoadrenocorticism Addisonian crisis: n Electrolyte abnormalities (hyperkalemia and/or hyponatremia); Shivering; Weakness; Reduced appetite/anorexia; Vomiting; Diarrhea Adrenal necrosis 7
Adrenal Steroidogenesis Cholesterol 3B-HSD Trilostane block Progesterone 17-OHP DHEAS 21-OH 3B-HSD 3B-HSD Aldosterone 21-OH Androstenedione Cortisol Testosterone Estrogen Trilostane Cerundolo et al, 2004 16 Poms and 8 Min Poodles with Alopecia X Hair re-growth: 14/16 (85%) Poms; 100% Min Poodles Dose:12 mg/kg and 9 mg/kg, respectively Re-growth occurred most often within 4-8 weeks In dogs that did not have hair re-growth at that time, the dose was doubled and re-growth occurred Cost: Pomeranian (3 kg) $80/mo; Malamute (50 kg) $563/mo 6 Months After Trilostane 8
Cyclosporine for Alopecia X? Cyclosporin prolongs the anagen phase of the hair cycle Cyclosporin inhibits the expression of Protein kinase C è stimulating hair follicle growth and hair fibre production HARMON et al., 1995 TAKAHASHI AND KAMIMURA, 2001 Rocky 8 weeks post-atopica Alopecia is not always a bad condition The Buddhist Monks of Xian 9
Recurrent seasonal flank alopecia Rhodesian Ridgeback atypical breed Recurrent seasonal flank alopecia Seasonal, recurrent Breed predisposition Airedale, Bulldog, Boxer Bilaterally symmetrical flanks hyperpigmentation Spontaneous regrowth 3-6 mths later Can become permanent Seasonal Flank Alopecia Diagnosis: R/O endocrinopathies Trichogram to evaluate for follicular dysplasia Clinical impression +/- Dermatohistopathology Very distorted hair follicles filled with keratin witches feet In a word, classic! 10
Seasonal Flank Alopecia Recurrent annually Fall and Spring +/- skip a year Melatonin imbalance Fall insufficient production Spring too much of a drop Minoxidil Vasodilator used topically in man androgenic alopecia Used orally in CRFA dogs regrew hair spontaneous??? side effects - weakness, lethargy, collapses 50% of the dogs treated Oral minoxidil NOT recommended Topical.we have other options Melatonin More Than a Jet Lag Pill Pineal gland è L-tryptophan è serotonin è melatonin Promotes IL-12 è Th-1 response Enhance IL-2 antitumor/cytotoxic lymphocytes pulsatile Hypothalamic LHRH Controls photoperiod-dependent molting/coat color via direct effects on hair follicles via pars tuberalis altered MSH and/or prolactin secretion 11
Melatonin Uses Recurrent Seasonal Flank Alopecia Alopecia X Pattern Baldness Melatonin More Than a Jet Lag Pill CRFA (50-75%), Canine Pattern Alopecia (50%+) Alopecia-X of the Nordic breeds (30-40%) Oral melatonin Injectable melatonin Implantable melatonin Peach fuzz in 4-6wks Maximal growth in 3-4 months +/- Lethargy, aggressiveness, Insulin resistance (not in DM) NOT w/neuropathies or breeding dogs The Oriental Pearl from the Bund Shanghai 2005 6 4 12
BBBTS Greyhounds Nonpruritic, noninflammatory alopecia Affects the caudal aspect of the pelvic limbs Can be progressive and involve the abdomen. BBBTS Greyhounds Non-specific hair growth promoters Pentoxifylline 10-30mg/kg TID Melatonin 1mg/kg divided TID Thyroxine 0.1mg/10lbs BID Cyclosporine Soft, warm bedding 13
Ischemic folliculopathies Pentoxifylline candidates 10-30mg/kg TID bald thigh/bald belly syndrome in greyhounds/whippets post-clipping traction alopecia elbow/hock calluses deep scarring pyoderma/pododermatitis CDA: Clinical Signs Normal at birth Gradual onset of dry, dull coat Alopecia on dorsum of trunk Progresses to partial/complete alopecia Hair regrowth is poor Poor quality of remaining hairs Usually most severe on trunk/colour diluted areas Often spares head, tail, limbs CDA: Clinical Signs Secondary superficial pyoderma May develop comedomes Skin usually becomes scaly Usually not pruritic Only if secondary infection 14
Dermatopathology CDA: Treatment Options No known specific treatment Hair growth promotion Melatonin 1mg/kg TID Help with epidermal barrier Vitamin A/synthetic retinoids Antiseborrheic/antibacterial shampoos Epidermal Barrier Repair Products Systemic antibiotics to treat secondary pyoderma n Oral/Injectable Remind owners that hair growth takes time Maximum 0.7 mm/day AFTER underlying etiology identified and addressed, it may take 10-12 weeks to see significant response 15
Bald is Beautiful. Questions? Ashtyn, Alyssa, Anthony, Andrea 16