{"id":1666,"date":"2016-10-26T14:07:35","date_gmt":"2016-10-26T14:07:35","guid":{"rendered":"http:\/\/phosdev.com\/todaysveterinarynurse\/?post_type=articles&p=1666"},"modified":"2022-02-22T20:08:10","modified_gmt":"2022-02-22T20:08:10","slug":"how-to-recognize-autoimmune-skin-disease-pemphigus-foliaceus","status":"publish","type":"post","link":"https:\/\/navc.sitepreview.app\/todaysveterinarynurse.com\/dermatology\/how-to-recognize-autoimmune-skin-disease-pemphigus-foliaceus\/","title":{"rendered":"How to Recognize Autoimmune Skin Disease: Tips for Spotting Pemphigus Foliaceus"},"content":{"rendered":"

Timely diagnosis of a medical condition is always in a patient\u2019s best interest. This is especially true when dealing with an autoimmune disease process, which has the potential to spiral out of control, have secondary infections develop, and even cause damage to other organ systems. Reaching a timely diagnosis can be quite a challenge with dermatology cases, since many diseases of the skin present so similarly at first glance.<\/p>\n

This article is intended to help veterinary technicians in general practice recognize key pieces of information in a patient\u2019s history, physical examination findings, and results of simple, in-house diagnostic tests that can help the healthcare team to narrow in on a diagnosis of pemphigus foliaceus (PF) at the patient\u2019s initial presentation.<\/p>\n

\n

Editor\u2019s Note:<\/strong> This article was originally published in November 2016. Please use this content for reference or educational purposes, but note that it is not being actively vetted after publication. For the most recent peer-reviewed content, see our issue archive<\/a><\/strong>.<\/p>\n

\n

Skin Health and the Immune System<\/h2>\n

Skin health is often a reflection of the health of a patient\u2019s immune system. When the immune system is robust\u2014barring the presence of infectious diseases and ectoparasites\u2014skin problems are rare. When the immune system is compromised, skin disease can run rampant. Skin disease can be further exacerbated by secondary infections, often creating a vicious cycle.1<\/sup><\/p>\n

Primary diseases that manifest when the immune system is not working well fall into two main categories: immune mediated and autoimmune.2<\/sup> Immune-mediated diseases are triggered by foreign antigens, such as drugs (including vaccines), infectious agents (e.g., bacteria, viruses), environmental substances, and food components.3<\/sup> Autoimmune diseases are caused by a failure of the immune system to recognize the patient\u2019s own antigens, or \u201cself,\u201d resulting in an attack by antibodies or lymphocytes against normal tissues. Autoimmune conditions also have a trigger that starts the disease process. However, the appearance of clinical signs may be delayed for as long as several months after the trigger event.1<\/sup> This can make searching for a trigger in a patient\u2019s history baffling. Difficulty is compounded by the fact that it is common for autoimmune disorders to have a history of waxing and waning clinical signs.1<\/sup><\/p>\n

There are many autoimmune dermatoses. The prognosis for each condition depends on the disease process. Some affect only the skin, while others, such as systemic lupus erythematosus,2,3<\/sup> can affect other organ systems, with serious consequences for the patient.<\/p>\n

Many dermatoses mimic each other because the skin displays only a limited number of reaction patterns.4<\/sup> As a result, there is no single dermatologic hallmark of autoimmune disease, but identifying lesions can help to narrow the differential diagnosis. For example, crusting is seen with PF, depigmentation with discoid lupus erythematosus,2<\/sup> and open fistulas with panniculitis.3 <\/sup><\/p>\n

Thorough examination of lesions is essential. For instance, a pustule associated with a superficial bacterial skin infection usually only incorporates one hair follicle, while pemphigus pustules span several follicles. At first glance, they look very similar, but paying attention to these details helps put the veterinarian on the right track for a diagnosis (FIGURES 1 and 2)<\/strong>.<\/p>\n

\"Figure<\/a>

FIGURE 2.<\/strong> Large pustules in pemphigus foliaceus. Image courtesy of Yu of Guelph Veterinary Dermatology<\/em><\/p><\/div>\n

\"FIGURE<\/a>

FIGURE 1.<\/strong> Small pustules in superficial pyoderma, with epidermal collarettes. Image courtesy of Yu of Guelph Veterinary Dermatology<\/em><\/p><\/div>\n

Other clinical signs commonly associated with autoimmune disorders are alopecia, erythema, purpura, vesicles, loss of skin architecture (due to the infiltration of plasma cells), and ulcers.1,2,5<\/sup> Notably, not many diseases involve the nasal planum, so if the nasal planum is affected, suspicion for an autoimmune disease such as pemphigus or lupus should be high.3,6,7<\/sup><\/p>\n

Pemphigus Foliaceus<\/h2>\n

The pemphigus complex is a group of uncommon autoimmune dermatoses characterized by acantholysis. Acantholysis is the breakdown of intercellular desmosomal bridges, deep in the epidermis, resulting in the release of individual, rounded keratinocytes that have large, dark-staining nuclei. These cells are known as acantholytic cells<\/em> (FIGURE 3)<\/strong>.<\/p>\n

\"FIGURE<\/a>

FIGURE 3.<\/strong> Acantholytic keratinocytes versus squamous epithelial cells at 100\u00d7 magnification. Image courtesy of Yu of Guelph Veterinary Dermatology<\/em><\/p><\/div>\n

PF is the most common condition of the pemphigus complex3,8<\/sup> and is the most frequently occurring autoimmune skin condition in dogs, cats, and horses. The disease usually appears to be idiopathic, although it has been associated with drug administration and can develop subsequent to chronic, usually allergic, skin disease.2<\/sup><\/p>\n

Other, rarer, forms of pemphigus include pemphigus vulgaris, pemphigus vegetans, pemphigus erythematosus, and paraneoplastic pemphigus. In some cases, neutrophilic and\/or eosinophilic infiltrate occurs throughout the epidermis in addition to acantholysis; the term panepidermal pustular pemphigus<\/em> has been suggested for this condition.9<\/sup><\/p>\n

Clinical Presentation and Diagnostic Differentials<\/h3>\n

Since many dermatologic conditions have a similar clinical presentation, breed predispositions can be very helpful in formulating a differential diagnosis.6<\/sup> For example, Akitas, Chow Chows, and English bulldogs are overrepresented breeds with PF,2<\/sup> although any breed can be affected. Animals are most often middle aged. The onset of clinical signs can be very rapid or very slow, with a history of waxing and waning being common. Patients with an acute onset may be depressed, anorexic, or febrile or have accompanying lymphadenopathy. Pain and pruritus are variable, and secondary bacterial infections may also be present.<\/p>\n

PF is a pustular disease, with primary lesions (pustules) starting as erythematous papules. The progression of lesions can be very rapid, and patients may present with widespread areas of pustules, yellow crusts, and erosions. Large pustules spanning multiple hair follicles are characteristic (FIGURE 4)<\/strong>.<\/p>\n

\"FIGURE<\/a>

FIGURE 4.<\/strong> Large pustule incorporating several hair follicles in pemphigus patient. Image courtesy of Yu of Guelph Veterinary Dermatology<\/em><\/p><\/div>\n

The pustular phase is followed by postinflammatory alopecia and epidermal collarettes, which can be extensive.2<\/sup><\/p>\n

The head, face, and pinnae are involved in more than 80% of cases, but lesions can progress to becoming generalized and more severe. Lesions are usually symmetrical. This distribution helps differentiate PF from staphylococcal pyoderma, in which the ventrum and trunk are affected without symmetry and cranial lesions are uncommon.2<\/sup> In dogs, the footpads are often affected with crusting that can lead to fissures.2<\/sup><\/p>\n

In cats, lesions on footpads are common and may be the only lesions present. Hallmarks of PF in cats include papular, crusting lesions around nail beds and nipples (FIGURE 5)<\/strong>.3<\/sup><\/p>\n

\"FIGURE<\/a>

FIGURE 5.<\/strong> Crusting of nail beds in a cat with pemphigus. Image courtesy of Yu of Guelph Veterinary Dermatology<\/em><\/p><\/div>\n

Nasal depigmentation can occur later in the course of the disease, unlike discoid lupus erythematosus, in which it is usually the first clinical sign noted (FIGURES 6 and 7)<\/strong>.2<\/sup> Oral or mucocutaneous lesions are very rare in PF but can be seen with pemphigus vulgaris and bullous pemphigoid.3<\/sup><\/p>\n

\"FIGURE<\/a>

FIGURE 7.<\/strong> Nose of a dog that has pemphigus foliaceus with crusting of nasal planum. Image courtesy of Yu of Guelph Veterinary Dermatology<\/em><\/p><\/div>\n

\"FIGURE<\/a>

FIGURE 6.<\/strong> Nose of a dog that has discoid lupus erythematosus (note loss of cobblestone appearance and depigmentation). Image courtesy of Yu of Guelph Veterinary Dermatology<\/em><\/p><\/div>\n

Differentials to rule out are numerous and include demodicosis, dermatophytosis (especially those caused by Trichophyton<\/em> spp), lupus (systemic lupus erythematosus, discoid lupus erythematosus), dermatomyositis, zinc- responsive dermatosis, cutaneous epitheliotrophic lymphoma, superficial necrolytic migratory erythema, other pemphigus diseases, leishmaniasis (in geographic areas where this disease is prevalent), and in cats, mosquito bite hypersensitivity.10<\/sup> If there is no obvious trigger event, a restricted diet trial should be considered, in the event that a food sensitivity is the culprit. Dietary triggers are well established in human medicine,11\u201314<\/sup> so a similar scenario for animals seems likely. In my experience, I have seen several cases of PF maintained in long-term remission with dietary restrictions.<\/p>\n

Diagnostic Tests<\/h3>\n

A tentative diagnosis can be readily made when typical clinical signs are present. Performing cytology and skin biopsies are the next steps in confirming PF.<\/p>\n

Cytology is invaluable when it comes to diagnosing PF, and it can be done quickly and easily in house. If the patient presents with crusts and pustules, a sample can be obtained by lifting a crust and performing an impression smear or by gently rupturing an intact pustule with a sterile, small-gauge needle and then making a touch prep with the contents (Tzanck smear). However, when an autoimmune skin disease is suspected, intact pustules are best left for biopsy samples.<\/p>\n

Processing samples for cytology is straightforward: slides should be air dried, then fixed and stained with Diff-Quik.<\/p>\n

Veterinary technicians who are familiar with assessing cytology samples can quickly identify acantholytic cells under the microscope even at lowest power. The presence of acantholytic keratinocytes surrounded by neutrophils is very suggestive of PF.3<\/sup> In these cases, acantholytic keratinocytes are often seen in \u201crafts\u201d (i.e., several cells close together). Examination of slides at higher magnification often shows that eosinophils are also present. Pemphigus is a sterile disease process, so bacteria are not usually seen, especially if performing a Tzanck smear on a large pustule that spans more than one hair follicle.<\/p>\n

Acantholytic keratinocytes can also be seen with deep pyoderma; however, bacteria are also seen in these cases. Acantholytic cells may also found with dermatophytosis (such as Trichophyton mentagrophytes<\/em>)9<\/sup> but are usually seen as single cells, as opposed to in rafts.<\/p>\n

Histopathologic evaluation of biopsy samples from intact pustules by a dermatohistopathologist is the gold standard for diagnosing PF. Classic histopathology is of a subcorneal pustule with acantholytic cells admixed with neutrophils and variable numbers of eosinophils.3<\/sup> Multiple punch biopsies should be obtained from representative lesions. If crusting is present, a crusted area should be chosen as a biopsy site, with the crust included in the sample. If pustules are present, a biopsy punch large enough to encompass an entire intact pustule should be chosen. Submission of ulcerated tissue is discouraged, as it will likely lead to a vague diagnosis of ulcerative dermatitis. Special stains can also be ordered, such as PAS (periodic acid\u2013Schiff staining) or GMS (Gomori\u2019s methenamine silver), which can help to rule out any autoimmune disease lookalikes, like dermatophytosis.<\/p>\n

Ideally, biopsy should be performed before an animal has started any corticosteroid treatment and after any secondary infections have been cleared.15<\/sup> Corticosteroids can disguise the disease process histologically and delay an accurate diagnosis. Biopsy sites should not be clipped or prepped, as this can remove crusts that often provide vital information for a dermatohistopathologist to make a diagnosis.<\/p>\n

Results of routine hematology and biochemistry tests are not diagnostic, but these tests should be run to establish baseline parameters before instituting immunosuppressive therapy. Neutrophilia is often present and may be severe.3<\/sup><\/p>\n

Treatment<\/h2>\n

There are two approaches to treating autoimmune dermatoses: immunosuppression and immunomodulation. The type of disease and the severity of the condition are what guide the veterinarian\u2019s choice of treatment. For instance, an animal with PF that has mild focal lesions on the pinnae may do well and be maintained on immunomodulatory drugs, while an animal with advanced disease and extensive lesions will need immunosuppressive therapy. The main benefit of immunomodulatory drugs is that they have less serious side effects than immunosuppressive treatments (TABLE 1)<\/strong>; however, all treatments carry the risk of adverse reactions.<\/p>\n

\"TABLE<\/a>

TABLE 1<\/strong> Immunosuppressive and Immunomodulatory Drugs<\/p><\/div>\n

If bacterial secondary infections are present, they should be treated with appropriate antibacterial therapy. If crusts or pustules have not resolved after a 4-week course of appropriate antibiotics, cytology should be repeated.3<\/sup><\/p>\n

Treatment Phases<\/h3>\n

There are 4 phases in the treatment of cutaneous autoimmune diseases: induction, transition, maintenance, and determining cure.2<\/sup><\/p>\n

The induction phase is meant to stop the inflammatory component as quickly as possible and suppress the immunologic response that is attacking the skin. During this phase, higher doses of medications are usually given. In general, immunomodulatory drugs take some time to be effective (around 3 to 4 weeks), so a high dose of glucocorticoids is often given initially to gain control of a disease. If a positive response is not seen in a timely manner, another treatment protocol will be considered. This could involve using alternative medications or adding medications to the current treatment protocol.<\/p>\n

In the transition phase, drugs are tapered to minimize adverse effects. When combinations of drugs are used, those with the most significant side effects (usually glucocorticoids) are the first to be tapered. Tapering is usually done slowly over several weeks or months, until an acceptable maintenance dose is reached or a relapse occurs. If relapse occurs, medications are increased until remission is achieved (i.e., the induction phase is repeated), then tapered down again to the last dose that kept the patient symptom free. This is the dose used for the maintenance phase.<\/p>\n

Depending on the trigger for the start of the disease, some patients may be completely weaned off both medications. A patient is considered cured once it has achieved remission, has been successfully controlled with maintenance therapy, and does not have recurrence after treatment has been stopped. However, most patients with PF require lifelong therapy to maintain remission.<\/p>\n

In severe cases, immunosuppressive drugs may be combined to achieve and maintain remission. Since many of these medications can have adverse effects on the liver and bone marrow, complete blood counts and serum biochemistry panels should be obtained every 2 to 3 weeks for the first couple of months. For maintenance, the monitoring frequency can be reduced to every 4 months or so. If blood work reveals adverse effects, the veterinarian may choose alternative medications.<\/p>\n

Other Treatment Considerations<\/h3>\n

Topical therapies are very useful for localized lesions and for managing flares. They include topical steroids and tacrolimus. Topical steroids allow the veterinary team to gain quick control over localized inflammation and lesions, but may result in thinning of the skin with chronic use. If long-term management is anticipated, switching the patient to tacrolimus can be beneficial. Topical shampoos can also be helpful in removing crusts.<\/p>\n

Stopping maintenance therapy in a well-controlled patient can be a little disconcerting, especially if the initial disease was severe. In many cases, maintenance therapy is continued for up to a year before considering discontinuation.2<\/sup> If the risk of recurrence outweighs the benefits of stopping treatment, protocols can be maintained lifelong with appropriate monitoring.<\/p>\n

Future vaccinations are usually discouraged in patients with autoimmune skin diseases, including PF, even in cases where vaccination is not a known trigger. The concern is that vaccination could cause a generalized immune response, possibly retriggering the autoimmune process.16<\/sup> In these cases, vaccine titers are recommended. If titer levels are insufficient, then a risk-benefit assessment should be done before considering vaccination.17<\/sup><\/p>\n

The prognosis for patients with PF varies according to the etiology and severity of disease but is considered to be fair to good.3<\/sup> Regular monitoring of clinical signs, complete blood counts, and serum biochemistry panels with treatment adjustments as needed is essential.<\/p>\n

Conclusion<\/h2>\n

There are many autoimmune skin diseases, with the most likely to be seen in general practice being PF. Veterinary technicians play a vital role in recognizing these patients, often being the first team members to take a patient history and do an initial physical examination. Being able to spot the clinical signs that point to pemphigus will help ensure that patients get a timely diagnosis and appropriate treatment.<\/p>\n","protected":false},"excerpt":{"rendered":"

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