sign in sign up
<<
Home , Acantholysis, Crust (dermatology), Pemphigus erythematosus, Pemphigus foliaceus, Pemphigus vegetans, Pemphigus vulgaris

VETERINARY NURSING EDUCATION

SKIN VERSUS FOLIACEUS AND THE AUTOIMMUNE GANG Lara Luke, BS, RVT, , Purdue Veterinary Teaching Hospital

This program was reviewed and approved by the AAVSB Learning Objective: After reading this article, the participant will be able to dis- RACE program for 1 hour of continuing education in jurisdictions which recognize AAVSB RACE approval. cuss and compare autoimmune that have dermatological afects, includ- Please contact the AAVSB RACE program if you have any ing (PF), (PE), Discoid comments/concerns regarding this program’s validity or relevancy to the veterinary profession. Erythematosus (DLE), Systemic (SLE). In addition, the reader will become familiar with diagnostic and treatment techniques.

FUNCTION OF THE SKIN Te skin is the largest organ of the body. Along with sensory function, it provides a barrier between the inside and outside world. Te is composed of the following fve layers: stratum basale, , stratum granulosum, stratum lucidum, and stratum corneum. Te stratum lucidum is found only on the nasal planum and footpads. When the cells of the epidermis are disrupted by systemic , the barrier is also disrupted. Clinical signs of skin disease will bring the patient into the veterinarian’s ofce for diagnosis.

32 THE NAVTA JOURNAL | NAVTA.NET VETERINARY NURSING EDUCATION

THE PEMPHIGUS COMPLEX article.3 Histologically it shares characteris- Pemphigus Foliaceus tics of both PF and DLE.1 This classifcation PF is an immune mediated pustular disor- is still considered controversial and PE may der included in a group of diseases known just be a localized variant of PF.1 as the pemphigus complex. It is one of fve recognized types in which the body Deeper Forms of the Pemphigus produces that target the proteins Complex binding the cells of the epidermis.1 It is The deeper forms of the pemphigus considered the number one autoimmune complex exhibit more serious signs. PV disease in dogs and cats, but has also been includes oral cavity and mucosal lesions. reported in humans, horses, and goats. Fever and anorexia often accompany der- matological signs. PVeg also includes oral are the proteins that bind lesions, but -like lesions and plaques (epidermal cells) to each can also be present. PPP is a deep form Figure 1 other. They are the target proteins in the of pemphigus associated with neopla- A 7-year-old M/N Cocker Spaniel with PF. pemphigus complex, which includes the sia, especially thymic lymphoma and superfcial diseases PF and pemphigus splenic sarcoma. There have only been erythematosus (PE), as well as the deeper two cases of canine PPP reported in the Ultraviolet light has been shown to trigger pemphigus diseases, literature and both are deceased. Immu- PF outbreaks. In addition, in the canine (PV), (PVeg), and nologic investigation of deceased patients patient, PF has been associated with such (PPP).3 When revealed that, as in the human form, the disorders as chronic skin disease, hypo- the desmosomes are untethered from presence of autoantibodies against mem- thyroidism, and systemic lupus erythema- each other, the breakdown of these con- bers of the plakin family were present.3 tosus (SLE).2 nections is called .3 Plakins are proteins involved in cellular development and tissue integrity.4 The DIAGNOSING PEMPHIGUS FOLIACEUS Clinical signs of PF are evident as pus- prognosis in humans is poor. Obtaining a cytology tules.2 Because the pustules are fragile If PF is on the doctor’s list of differentials, and rupture easily, they may not be visible Causes Of Pemphigus Foliaceus diagnosing the condition involves cytology on physical examination. The patient There are several factors that may play a and histopathology. It is ideal to obtain may present only with epidermal collar- part in the development of PF, although the an impression smear from the material of ets from the ruptured pustules, as well as specifc predisposing trigger may not be an intact pustule. Using a sterile needle, crusts, scales, and erosions.5 In the canine found in most cases.3 The frst cause often rupture the pustule and press a glass patient, of the footpads considered is genetics. In canines, different slide against the exudate. Pustules are may also be evident (Fig 1). papers have listed several different breeds fragile and rupture easily, so they may be reported with the disease. However, it can rare on physical exam. If only one pus- In felines, clinical signs of PF are similar be agreed upon that the two breeds over- tule is found, save that for histopathology. to dogs with lesions covering the pinnae, represented are Akitas and Chow Chows. Material can be obtained from beneath any periocular regions, and footpads. Like the Cats and horses have not proven any or collarette. Heat fx the slide and dog, it can become generalized. In cats, breed predilection.2,5 Similarly, evidence of stain with Diff-Quick stain. the claw folds can also be involved. Horses breed predilection for PF is missing in the tend to have a more generalized pattern of author’s search of goat literature. The hallmark of PF is the presence of crusting, scaling, and alopecia. In caprine acantholytic keratinocytes (Fig 2). These patients, it is reported generalized over the Drugs have been implicated in trigger- are the immature cells of the epidermis body and the teats in females.1 ing PF. This happens when the drug whose desmosomes have been broken. induces acantholysis, activates proteolytic They have the appearance of rounded, Pemphigus Erythematosus enzymes that disrupt desmosomes leading darkly stained cells with prominent nuclei. The more benign form of the superfcial to acanthoylsis, or stimulates autoantibod- Other fndings can include nondegener- pemphigus complex, PE, generally limits ies against the desmosomes. Some drugs ated neutrophils and eosinophils.2 These clinical signs to the facial region, including that may be implicated are cephalexin, fndings are highly suggestive of PF, but depigmentation of the nose. Some consider amoxicillin, clavulanic acid, and cimetidine. dermatophytosis and pyoderma can also it to be a crossover between PF and dis- It is often diffcult to prove which drug in present with these cytological fndings. coid lupus erythematosus (DLE). Lupus ery- the patient’s history is at fault.2,3 This must be ruled out with a fungal thematosus will be discussed later in this culture because the immunosuppressive

VETERINARY NURSING IN ACTION | JUN/JUL 2017 33 VETERINARY NURSING EDUCATION drugs used to treat PF are not recom- Treatment Options For mended for dermatophytosis.2 Pemphigus Foliaceus

Histopathology For mild cases of PF, topical glucocorti- A biopsy should be submitted (ideally) to a coids (GCs) can be used to treat lesions. dermatohistopathologist for fnal diagno- Topical steroids can cause skin , sis of PF. A 6mm punch biopsy of at least so the patient must be monitored. For three different sites is recommended. If more severe cases, systemic GCs are the an intact pustule and/or crust is included, most common treatment. Because cats it is ideal. Equipment needed is a 6mm don’t metabolize prednisone as well as punch biopsy, a formalin jar, iris scissors dogs, they should be prescribed pred- or a scalpel, and forceps. A permanent nisolone. It is not recommended to use Figure 3 marker is used to circle the lesion of inter- injectable long acting GCs. The veterinarian A 6-year-old Australian Shepherd with DLE. est. Some of the instruments used will be needs to be able to adjust the dose based dependent on the personal preference on the patient’s response. Common side In one case, a Nigerian Dwarf goat kid of the doctor performing the procedure. effects observed include polyuria, polydip- developed PF at the age of two months. Amount of bleeding will depend on the sia, and polyphagia. Other, more serious Four weeks after treatment with GCs, site from which the biopsy is taken, so be side effects that can develop are iatrogenic she was still showing signs of fever, even prepared with gauze sponges. The site is Cushing’s disease, gastric ulcers, and dia- though her skin was improving. Gold closed with a non-absorbable or absorb- betes mellitus.2 salts were added to her therapy. The GCs able suture. If the dog is awake, a local were able to be decreased with time and block of approximately 1ml of 2% lido- GCs alone are often not enough to control eventually discontinued. After six months caine is used for analgesia. clinical signs of PF. can be of receiving gold salts, this treatment was used along with GCs or used alone once also able to be discontinued.6 This procedure is clean but not sterile, so it takes effect. It must be noted that this surgical gloves are not required; however, can take weeks, so the veterinarian may LUPUS ERYTHEMATOSUS exam gloves should be worn. Any hair can choose to keep the patient on GCs during Discoid lupus erythematosus be clipped with a pair of scissors, but care that time. Potential side effects of Azathi- A differential diagnosis for PF is Lupus Ery- should be taken not to disturb the crusts aprine can include bone marrow suppres- thematosus. Discoid Lupus Erythematosus or damage the skin. The site should not be sion, hepatotoxicosis, pancreatitis, and GI (DLE) is a fairly benign condition that may prepped as the crusts contain many of the signs, such as vomiting or diarrhea.2 It is be aggravated by ultraviolet light exposure. cells pathologists use to make a diagnosis. important to perform a CBC and chemistry This may be the second most common After the veterinarian has taken the samples, profle regularly to monitor organ function. in dogs. One of the they should be blotted and placed in formalin. Azathioprine is not recommended in cats. frst clinical signs noticed may be a change to the appearance of the nose, which will Histopathological fndings are similar in Feline patients not responsive to GCs lose its pigment and the structure becomes all species. The primary fndings are the will often respond to Chlorambucil, an smooth (Fig 3). Progression can lead to presence of multiple acantholytic kerati- alkylating agent. Side effects include GI crusting and scaling, migrating up the nasal nocytes, corneal and subcorneal pus- signs and myelosuppression, so regular planum to the eyes and the ears. For some tules, a large number of neutrophils, lab work is recommended. dogs, the footpads, limbs and perianal and a few eosinophils.1 regions can be affected3 (Fig 4). In cats, DLE Some patients respond to niacinamide is rarely reported. Clinical signs are often combined with tetracycline or doxycycline restricted to the face and the ears.3 This is to suppress the immune system. a fairly benign form of lupus and prognosis For patients with mild cases of PF, it can is good. Treatment involves use of immuno- be used as the sole treatment, but this suppressive drugs; however, patients can combination can also be used in conjunc- achieve remission and remain off GC’s with tion with azathiaprine or GCs for more use of Tetracycline or doxycycline with nia- severe cases.2 cinamide. Vitamin E may be recommended as well. If possible, limiting the patient’s exposure to UV light will decrease chances 3 Figure 2 of fare up due to such exposure. Acantholytic keratinocytes shown on cytology.

34 VETERINARY NURSING EDUCATION

Breed Specific Forms of Lupus Treatment Options For SLE addition, these patients may have defec- Erythematosus tive T-suppressor cells.9 Breed type may As with other autoimmune diseases, treat- Two forms of lupus worth mentioning are have some infuence. Reported breeds ment of SLE often includes GC’s which breed specifc. Vesicular cutaneous lupus thought to be predisposed include German may be used along with drugs such as erythematosus (VCLE) is primarily found shepherds, Shetland sheepdogs, collies, azothiaprine or chlorambucil. Other drugs, in middle-aged to older rough collies and beagles, and poodles. Forty to ffty percent including the chemotherapeutic medica- Shetland sheepdogs. This disease is typ- of cases may develop skin lesions similar tion Vincristine, have been used, depend- ically limited to ulcerative dermatological to DLE with lesions not restricted to the ing on clinical manifestations presented by signs. Clinical signs are aggravated by head region.3 Cutaneous signs can range increased UV exposure. Histological fnd- from mild seborrheic dermatitis to severe ings are similar to systemic lupus erythe- and widespread ulceration and can include matosus (SLE).3 hyperkeratotic footpads.10 The nose and periocular regions may lose pigment. The The German shorthaired pointer is afficted nasal region may also present as erythem- with exfoliative cutaneous lupus erythe- atous and ulcerative with crusts formed. matosus (ECLE). These dogs tend to Areas of the body exposed to light are develop the disease at an early age. ECLE more susceptible to lesion formation and is characterized by scaling and alopecia so UV light may play a role in the disease around the head region and trunk of body. process. Other clinical signs that may Ulceration may also be present in severe accompany SLE, though not an exhaus- cases. The patient may also present with tive list, are joint disease, hematologic generalized pain or pain localized to a changes, glomerulonephritis, neurological Figure 4 joint, though this is not the same as the abnormalities, and fever. The fever is non- Hyperkeratosis of the footpad on a joint disease that can present with SLE. responsive to , but decreases 6-year-old M/N Labrador Retriever with DLE. Histopathology has some similar charac- with administration of GCs.3 teristics to SLE; however, there is evidence patients. Each case is unique and so the of sweat and sebaceous glands. Also Diagnosing SLE combination of therapies will need to ft included is the presence of T lymphocytes Diagnosing SLE is not easy because there the individual. Prognosis is poor.3 involved in interface dermatitis.3 are a large number of possible clinical signs that must be worked up and other SLE In Other Species SYSTEMIC LUPUS ERYTHEMATOSUS disorders ruled out. Histopathology and This condition is rare in cats, but they can The most severe form of Lupus Erythema- presence of four of the criteria or clinical develop drug induced lupus.8 Methimazole tosus, SLE, has been reported in humans, signs, such as arthritis, discoid rash, and and carbimazole, used to treat hyper- dogs, and cats. SLE attacks various inter- antinuclear antibodies, are needed to thyroidism, have immune-mediated side nal systems, particularly the joints, as well diagnose SLE.3 effects and have been implicated. Equally as the skin. While uncommon in dogs and rare, only two horses have been described rare in cats, the severity of the disease is Histopathology in the literature to have been diagnosed worth further discussion.3,7 As with the pemphigus complex, it is with SLE. important to send in biopsy samples to a Causes Systemic Lupus dermatohistopathologist. Samples should Conclusion Erythematosus be taken by the same method as sam- When presented with more complex der- While the underlying cause of SLE is not ples collected for PF; however, in some matologic disorders, it is always import- completely understood, it is thought to cases, a 4mm punch may be a better size, ant to investigate all possible underlying result from a Type II and Type III hyper- depending on area of sampling. Hydropic causes. Many autoimmune diseases have sensitivity. The delayed reaction Type IV degeneration, or intracellular edema of the dermatological signs. A thorough exam- may play a part as well. The body devel- basal cells in the basal layer of the epider- ination and history are important in the ops antibodies to specifc tissue proteins. mis, is one fnding. The boundary between process of diagnosing a primary disorder. Tests can be run to look at the immune the and epidermis can become Following through with diagnostic proce- response. For example, CD4 and CD8 undefned.11 There may be evidence of dures such as cytology and histopathology are two types of lymphocytes. CD4 fghts apoptotic keratinocytes, or cell death. is an important part of diagnosing these infection while CD8 attacks cancer cells.8 Loss of melanin from the epidermis, or diseases. The information obtained will The ratio between these two lymphocytes pigmentary incontinence of the epidermis, assist in the development of treatment tends to increase in dogs with SLE. In is another histopathological fnding. plans for these patients.

VETERINARY NURSING IN ACTION | JUN/JUL 2017 35 VETERINARY NURSING EDUCATION

REFERENCES 1. Olivry T. A review of autoimmune skin diseases in Article Questions domestic animals: I-Superficial pemphigus, European Society of Veterinary Dermatology. 2006; 17; 1. What is the largest organ 4. Vesicular Cutaneous Lupus 291-305 in the body? Erythematosus is primarily found in: 2. Tater K, Olivry T. Canine and feline pemphigus a. Large Intestine a. Middle-aged to older foliaceus: Improving your chances of a successful b. Heart rough collies outcome. http://veterinarymedicine.dvm360.com/ c. Skin b. Young Shetland canine-and-feline-pemphigus-foliaceus-your-chanc- d. Liver sheepdogs es-successful-outcome c. Cats 3. Miller WH, Griffen CE, Campbell KL. Autoimmune 2. All of the following are d. German Shepherds and Immune-Mediated Dermatosis. In: Muller & layers of the skin, except: Kirk’s Small Animal Dermatology 7th edition. St. a. stratum basale Louis, MO: Elsevier Mosby; 2013; 432-500 5. Which of the following b. stratum spinos process aggravates Lupus 4. Leung CL, Green KJ, Liem RK. Plakins: a family of c. stratum granulosum Erythematosus? versatile cytolinker proteins. Trends Cell Biol. 2002 d. stratum corneum a. Food preserved with Jan; 12(1):37-45 Vitamin E 5. Zabel S, Mueller RS, Fieseler KV, Bettenay SV, b. UV exposure Littlewood JD, Wagoner R. Review of 15 cases of 3. Systemic Lupus Erythematosus c. Excess water intake pemphigus foliaceus in horses and a survey of the is common in: d. Neoplasia literature. Veterinary Record.2005; 157;505-509 a. Cats 6. Cornish J, Highland, M. Successful treatment of b. Quarter Horses juvenile pemphigus foliaceus in a Nigerian Dwarf c. Poodles goat. JAVMA.2010;236(6)674-676 d. Elephants 7. Hnilica KA. Autoimmune and Immune-Mediated CONTINUING EDUCATION Skin Disorders. In: Winkel A, ed. Small Animal QUIZ ONLINE Dermatology: A Color Atlas and Therapeutic Guide visit VetMedTeam.com 3rd edition. St. Louis, MO: Saunders Elsevier; and log in with your 2011:227-282 Vet Med Team Profle. 8. Sather R, Snyder M. CD4-CD8 Ratio. Health Encyclopedia. University of Roch- ® ester Medical Center. https://www.urmc. rochester.edu/encyclopedia/content. aspx?contenttypeid=167&contentid=cd4_cd8_ratio 9. Nelson WN, Couto CG. Common Immune-Medi- ated Diseases. In: Small Animal Internal Medicine 5th edition. St. Louis, MO: Elsevier Mosby; 2014: Lara Luke, BS, RVT, Dermatology, Purdue Veterinary Teaching Hospital 1417-1440 10. Day MJ. Systemic Lupus Erythematosus in Lara is the dermatology/internal medicine technician at Purdue University. She received Domestic Animals. In: Systemic Lupus Erythe- her B.S. at Texas A&M in wildlife ecology in 1994. In 1998 she earned an associates degree matosus. Bristol, UK. Jai-Elsevier Science Inc; in veterinary technology at Purdue University. After a few years in mixed animal private 2011:437-451 practice, Lara returned to Purdue in 2004. In 2013 she joined the internal medicine team with primary duties working in dermatology. When not at work Lara enjoys life with her 11. Gross, TL, Ihrke PJ, Walder EJ, Affolter VK. Inter- three Alaskan Klee Kai. She is involved with conformation and rally obedience and hopes face dieseases of the dermal-epidermal junction. to start the dogs in barn hunt and agility. She is involved with the Greater Lafayette Kennel In Skin Diseases of the Dog and Cat Clinical and Club and helps teach conformation classes. Histopathologic Diagnosis 2nd edition. Oxford, UK: Blackwell Publishing; 2005:49-74

36 THE NAVTA JOURNAL | NAVTA.NET