Derm 13 - immune diseases

Question 1

dematologic immune-mediated diseases
- how common?
- easily diagnosed?
- when should we intervene?

Answer 1

 Uncommon to Rare
 Oftentimes over suspected or missed
 Early intervention may lead to faster control
> On the other hand, overdiagnosis of immune mediated disease leading to immunosuppressive treatment of a patient with a poorly responsive parasitic, bacterial or fungal disease could be disastrous!

Question 2

most common immune skin disease seen in clinical practice

Answer 2

Pemphigus Foliaceus (PF)/ Pemphigus Erythematosus (PE)

Question 3

Pemphigus Foliaceus (PF)/ Pemphigus Erythematosus (PE) in the dog
- etiology
- relationship between these conditions?
- occurrence
- how cells are affected
- lesion appearance and distribution

Answer 3

• This is a disease that results from a pathological loss of adhesion between keratinocytes secondary to immune attack on the desmosome, the links between the corneocytes of the skin
  > In dogs, it is highly suspicious that the target antigen is desmocollin-1, especially in facial predominant cases.
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• PE is considered by many these days to be a milder form of PF (It was once considered a crossover disease between PF and DLE)
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• Can occur spontaneously or can be associated with tumors or drug administration
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• Desmosomal attack results in the formation of rounded keratinocytes, or acantholytic keratinocytes (not acanthocytes)
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• In dogs this results in a pustular dermatitis often associated with honey coloured crusts
  > can be confused with a pyoderma. However, in general, the lesions appear more generalized and pustular compared with pyoderma cases
• Trunk and head (including pinnal) distribution is common; footpads are affected in 35% of cases
• Lesions are restricted to the face in 16-24% of cases and 58% progress to include the trunk.

Question 4

Pemphigus Foliaceus (PF)/ Pemphigus Erythematosus (PE) in the dog
- Dx?
- what else should we consider?

Answer 4

• presence of acantholytic keratinocytes are highly suggestive of a diagnosis.
  > However, the presence of these cells in small numbers is not pathognomonic for PF
  > Indeed dermatophytosis (trichophyton spp.) and bacterial infection can also result in acantholytic keratinocytes (AK’s)
• The presence of bacteria along with a small number of AK’s on cytology should lead one to begin antibiotic treatment (+/- bacterial culture) before considering pemphigus
• Fungal culture should be routinely performed as well in patients slated for biopsy

Question 5

Pemphigus Foliaceus (PF)/ Pemphigus Erythematosus (PE) in the dog
- signalment

Answer 5

• Middle age – mean age of onset 4-6 years but can occur at any age
• Breed predisposition:
  ◦ Akita, Chow Chow overrepresented but also seen commonly in Cocker Spaniel, Dachshunds and Labrador Retrievers but can be any breed

Question 6

conditions that look like pemphigus

Answer 6

• dematophytosis
• pyoderma

Question 7

PF treatment vs biopsy - which should we do first and why?

Answer 7

I will treat patients with antibiotics for at least 2 weeks before performing a biopsy. It is not uncommon for patients with PF to have secondary infections and the presence of infection in the biopsy sample will complicate the diagnosis
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- Tx with antibiotics before Bx
> improved success rate? fewer euthanasias?
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The long term benefit of treating PF patients with antibiotics before or when starting treatment is controversial. It was reported to improve outcome, but in a more recent reviews by Mueller, there were no significant differences in success rate with early antibiotic treatment
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- culture a biopsy
- collect multiple samples

Question 8

PF treatment
- glucocorticoid success?
- azathioprine and prednisolone?
- prednisolone alone?

Answer 8

• not much difference between any of these

Question 9

PF success rate with exclusive glucocorticoid therapy? prognositc sign?

Answer 9

<50%, with a favorable response within the first 10 days of treatment being a good prognostic sign

Question 10

PF treatment with immunosuppression success rate?

Answer 10

• 52% went into remission with treatment
• 35% improved greatly but still had focal lesions
• 13% euthanized

Question 11

PF most common treatment? dosing?

Answer 11

• Most commonly, prednisone or prednisolone is administered at immunosuppressive dosages
• lately the tendency is not to use the top end doses in most cases
• divide the dose into 2 treatments BID
• If a favorable response is seen within 10–14 days this dosage is reduced to SID
• If the response continues to be very good, I will decrease doses by 25% for 28 days and then lower to an alternate day basis with the goal of dosing at 1 mg/kg every 48 h or less

Question 12

PF treatment for ‘stubborn spot’

Answer 12

I have found 0.1% tacrolimus to be very useful for stubborn spots / localized cases

Question 13

alternate steroids vs prednisone for PF?

Answer 13

• Too PU/PD? Consider drugs with less mineralocorticoid activity
  > methylprednisolone at similar dosage
• Dexamethosone more potent, but watch out for side effects (GI bleed)

Question 14

What can we do if we are treating PF and there is a poor / inadequate response to steroids?

Answer 14

• start azathioprine in the dog (do not use azathioprine in the cat.)
• Chlorambucil for cats

Question 15

adverse reactions to azathioprine

Answer 15

• Hepatotoxicity
• pancreatitis
• Myelosuppression (lymphopenia, anemia and leukopenia)
• Diarrhea (which can be severe and lead to discontinuation of the drug)
• Increased susceptibility to opportunistic infection when used long term
  > pyoderma, demodicosis, dermatophytosis
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  Thiopurine methyltransferase
• metabolizes AZA
  > 0.8% of population have low levels and are susceptible to bone marrow dyscrasias
  > some have too much and need a higher dose

Question 16

monitoring patients on Azathioprine

Answer 16

CBC and liver profiles, every 2-3 weeks, then every 3-6 months once in remission

Question 17

apoquel for PF - does it work?

Answer 17

• Good response with 72.7%
• You can see clinical improvement within 2 week
• can start while awaiting biopsy results

Question 18

Tetracycline/Niacinamide use for PF

Answer 18

• useful treatment regime for patients with Pemphigus erythematosus, when the response to tacrolimus is inadequate or the lesions are in locations where I am less comfortable utilizing tacrolimus
• also as a steroid sparing agent for patients that start to relapse when the steroid doses gets too low
• Antimicrobial stewardship is a consideration and should be a topic of discussion these days when using an antibiotic chronically for immune modulation

Question 19

Pemphigus Foliaceus (PF) in the cat
- how common
- easily diagnosed?

Answer 19

• Uncommon to Rare
• often over- suspected; on the other hand, is can often be missed
• appropriate diagnosis and early intervention may lead to faster control

Question 20

Pemphigus Foliaceus (PF) in the cat
- presentation, rule out

Answer 20

• The head, face and ears are commonly affected.
• A significant percentage of cats with pemphigus have claw fold involvement; it is important to rule out bronchogenic adenocarcinoma which can mimic this presentation.

Question 21

Pemphigus Foliaceus (PF) in the cat
- treatment response, duration
- age of onset
- treatment
- what if poor response?

Answer 21

• most cats with PF respond favorably to treatment, but they require long term treatment
• median age of onset at presentation = 6 years
• long term immunosuppression
  > Corticosteroids alone work in many cases, with a reported 62-100% response rates
  > prednisolone
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• I will consider dexamethasone if the response is inadequate, even though I feel it has a better response rate.
  > Why? In a pilot study comparing the diabetogenic effects of dexamethasone and prednisolone in cats,“preliminary data suggest that dexamethasone exhibits greater diabetogenic effects in cats than equipotent doses of prednisolone.
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• What if there is a poor or inadequate response to steroids?
  > In cats whose PF fails to respond to glucocorticoids, chlorambucil has historically been the most common drug added
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• can use cyclosporine to wean off of glucocorticoids

Question 22

Canine Discoid/Cutaneous lupus Erythematosus
- how common?
- presentation

Answer 22

• Common
• No involvement of other body tissues
• ANA negative (antinuclear antibody
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• Crusts, erosions and planum leading to ulcers on the nasal planum leading to depigmentation and a
  loss of the typical cobblestone appearance of the
  nose
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  Mucocutaneous pyoderma can present
  similarly to discoid lupus and is very
  difficult to distinguish histopathologically!
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• Therefore all patients should be on a course of antibiotics before and at the time of biopsy

Question 23

Canine Discoid/Cutaneous lupus Erythematosus treatment

Answer 23

• 0.1% tacrolimus. I treat twice a day for the first 2 months and then decrease treatment to once daily
• Patients should be discouraged from licking their nose after application
• short course of steroid such as betamethasone, amcinonide, or fluocinole may help things get under control until maintenance with tacrolimus can be achieved
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• These patients should avoid the midday sun as this appears to be an exacerbating factor for both this disease and pemphigus. Topical sunscreens can be applied if sun avoidance is not possible
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• reported success with off-label use of oclacitinib in some cases
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• Tetracycline and Niacinamide is an effective treatment in many cases where topicals cant be used

Question 24

the most common disease that affects only the claw
- typical distribution?

Answer 24

Lupoid onychitis
o aka Symmetric Lupoid Onychodystrophy
o should be high on the list of differentials whenever there is onychodystrophy or onychomadesis of
multiple claws on multiple paws

Question 25

lupoid onychitis possible association with what diseases?

Answer 25

• patients on thyroid therapy
• adverse food reaction?

Question 26

Lupoid onychitis treatment options

Answer 26

• fatty acid supplementation may have some benefit
  > 3/6 combination products for LO
• Most cases require concurrent therapies and my use of fatty acid supplementation tends to be adjunctive
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• respond to the combination of tetracycline and niacinamide
• if ineffective: prednisone and azathioprine may be indicated

Question 27

Lupoid onychitis
- diagnostic process
- treatment process

Answer 27

• diagnosis and treatment of suspected cases should include cytology and bacterial culture
  to rule out a secondary infection, thyroid function should be assessed, and a food trial performed. A biopsy to rule out pemphigus foliaceus or other immune mediated disease may be indicated in some cases
• Histopathological confirmation of the disease requires amputation of the 3rd phalanx of an affected digit > declaw
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• dermatologists treat presumptively before performing this procedure
• If there is no response to antibiotics, treatment with fatty acids, tetracycline and niacinamide q8h for a period of 8 weeks +/- a food trial is recommended
• If the response is inadequate, addition of pentoxifylline to the regime is indicated for an additional 8 weeks before considering prednisone and azathioprine