Causes of alopecia Folliculitis Dermatophytosis

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1 THERAPEUTIC APPROACH TO AUTOIMMUNE SKIN DISEASES IN VETERINARY DERMATOLOGY Anthony A. Yu DVM, MS, ACVD Guelph Veterinary Specialty Hospital 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

2 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

3 Cushing s Syndrome Pituitary Tumor Lysodren 25-50mg/kg 1-3X/week Trilostane 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 mg/kg BID ACTH 4-6h post Trilostane 10d, 4wks, 3mos, 6-12 mos goal post-acth = 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

4 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

5 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

6 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

7 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

8 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, 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

9 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

10 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

11 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

12 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

13 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

14 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

15 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 weeks to see significant response 15

16 Bald is Beautiful. Questions? Ashtyn, Alyssa, Anthony, Andrea 16