37, 38: Pyoderma Gangrenosum, Subcorneal Pustular Dermatosis (Sneddon-Wilkinson Disease)

Question 1

What is the initial presentation of Pyoderma Gangrenosum?

Answer 1

The initial presentation of Pyoderma Gangrenosum is a painful nodule, plaque, or pustule that enlarges and breaks down to form a progressively enlarging ulcer with raised, undermined, violaceous borders and a surrounding zone of erythema.

Question 2

What percentage of Pyoderma Gangrenosum cases are associated with underlying systemic diseases?

Answer 2

Approximately 70% of Pyoderma Gangrenosum cases are associated with underlying systemic diseases such as IBD, monoclonal gammopathy, and hematologic diseases.

Question 3

What are the common sites for the different variants of Pyoderma Gangrenosum?

Answer 3

The common sites for the different variants of Pyoderma Gangrenosum are as follows:

• Ulcerative: Leg
• Bullous: Upper limbs
• Pustular: Trunk (lesser extent: face and limbs)
• Vegetative: Trunk

Question 4

What is the pathergic phenomenon in relation to Pyoderma Gangrenosum?

Answer 4

The pathergic phenomenon refers to the occurrence of Pyoderma Gangrenosum lesions at the site of trauma or surgery, where trauma or irritation can induce exaggerated flaring of the condition.

Question 5

What are some complications associated with therapeutic interventions for Pyoderma Gangrenosum?

Answer 5

Complications from therapeutic interventions for Pyoderma Gangrenosum include:

• Corticosteroids: can induce or worsen diabetes
• Cyclosporin: can worsen renal dysfunction
• Immunotherapy: can lead to immunocompromise

Additionally, elective surgery should be undertaken with caution due to the possibility of inducing new PG lesions.

Question 6

What is the initial step in management for a patient diagnosed with Pyoderma Gangrenosum?

Answer 6

The initial step in management involves clinical diagnosis after excluding other causes, followed by wound care and systemic corticosteroids if necessary.

Question 7

What is the likely variant of Pyoderma Gangrenosum in a patient with ulcerative colitis and multiple painful pustules on the trunk?

Answer 7

The likely variant is the pustular form of Pyoderma Gangrenosum, which occurs exclusively during acute exacerbations of IBD. Management involves controlling the underlying IBD, potentially requiring bowel resection.

Question 8

What phenomenon occurs when a patient develops exaggerated flaring of skin lesions at the surgical site?

Answer 8

This is the pathergic phenomenon, where trauma induces exaggerated flaring. Prevention includes close supervision by a dermatologist and possibly systemic steroids during and after surgery.

Question 9

What complications should be considered for a patient with a history of Pyoderma Gangrenosum presenting with severe pain and loss of mobility?

Answer 9

Complications to consider include severe pain, loss of mobility, anemia of chronic disease, and complications from therapeutic interventions like corticosteroids or cyclosporin.

Question 10

What are the key characteristics of the ulcerative variant of Pyoderma Gangrenosum?

Answer 10

• Intensely painful erythematous papule, pustule, or nodular furuncle (usually single, may be multiple)
• Surrounded by a zone of erythema
• Central degeneration leads to an eroding ulcer
• The ulcer has a bluish/violaceous undermined edge and purulent necrotic material at the base
• May expose muscle or tendon in some cases
• Erupts on normal-looking skin
• Most common site: leg
• Can occur at sites of trauma or surgery (pathergic phenomenon).

Question 11

What is the clinical significance of the bullous variant of Pyoderma Gangrenosum?

Answer 11

• Known as atypical PG
• Characterized by painful, rapidly expanding superficial inflammatory blisters that quickly erode
• The roof of the blister undergoes rapid necrosis, requiring close inspection to reveal its bullous nature
• Most common site: upper limbs
• Often associated with hematologic disease
• May show clinical and histologic overlap with Sweet syndrome.

Question 12

How does the pustular variant of Pyoderma Gangrenosum relate to inflammatory bowel disease (IBD)?

Answer 12

• Known as pustular eruption of IBD
• Occurs exclusively during an exacerbation of acute IBD (usually ulcerative colitis)
• Characterized by rapid development of multiple, large, painful pustules on the trunk, face, and limbs
• Control of pustular lesions is difficult without managing the underlying IBD, which may require surgical intervention.

Question 13

What are the potential complications associated with therapeutic interventions for Pyoderma Gangrenosum?

Answer 13

• Severe pain
• Loss of mobility
• Anemia of chronic disease
• Complications from medications:
  
  1. Corticosteroids – can induce or worsen diabetes
  2. Cyclosporin – may worsen renal dysfunction
  3. Immunotherapy – can lead to immunocompromise
• Elective surgery should be approached with caution due to the risk of inducing new PG lesions (pathergic phenomenon).

Question 14

What are the key inflammatory mediators involved in the pathogenesis of Pyoderma Gangrenosum (PG)?

Answer 14

Key inflammatory mediators involved in PG include:

• TNF-α: Promotes the production of proinflammatory cytokines and enhances neutrophil degranulation.
• IL-8: A potent neutrophil chemotactic agent.
• IL-7: A pro-inflammatory cytokine that stimulates expression of IL-8 and G-CSF.
• MMP-2/MMP-9: Collagenases that mediate tissue damage.
• T-cells: Involved in cytokine signaling and antigenic stimulus, contributing to aberrant neutrophil activity.

Question 15

What genetic mutations are associated with PAPA syndrome and its variants?

Answer 15

PAPA syndrome and its variants are associated with the following genetic mutations:

• PSTPIP1: Mutations lead to decreased inhibition of the inflammasome and increased production of IL-1β and IL-18.
• JAK2: Mutations are linked to inflammatory and myeloproliferative disorders.
• MTHFR: Mutations in methylenetetra-hydrofolate reductase are also noted.
• Familial cases may occur without specific reported mutations, and cases may be associated with inflammatory bowel disease (IBD), polyarthritis, and hematologic diseases.

Question 16

What are the major criteria for diagnosing Pyoderma Gangrenosum (PG)?

Answer 16

The major criteria for diagnosing Pyoderma Gangrenosum (PG) include:

1. Sudden onset of a painful lesion with characteristic morphology in a patient without fever, significant toxemia, or relevant drug intake.
2. Histopathologic exclusion of significant vasculitis, malignancy, and infective organisms through special histologic studies/stains and negative tissue cultures, as well as exclusion of significant vascular stasis/occlusion by appropriate studies.

Question 17

What hormonal influences are associated with Pyoderma Gangrenosum?

Answer 17

Hormonal influences associated with Pyoderma Gangrenosum include:

• Hidradenitis suppurativa and acne: These conditions are known to occur with PG in some patients, often with reports of premenstrual flares.
• A case of PG with premenstrual flares was controlled using a combined oral contraceptive and antiandrogen.
• Elevated levels of IL-17 and TNF-α have been observed in lesional skin of patients with hidradenitis suppurativa, acne, and PG, which also show a positive response to TNF-α inhibitors.

Question 18

What does a biopsy showing CD3+ T cells and CD163+ macrophages at the wound edge indicate about the pathogenesis of Pyoderma Gangrenosum?

Answer 18

This indicates that T cells and macrophages play a role in the pathogenesis through cytokine signaling and antigenic stimulus, contributing to neutrophil recruitment.

Question 19

What is the significance of elevated serum levels of TNF-α and IL-6 in a patient with Pyoderma Gangrenosum?

Answer 19

Elevated TNF-α and IL-6 levels correlate with ulcer activity and indicate an inflammatory response driving the disease.

Question 20

What syndrome is associated with a genetic mutation in PSTP1P1, and what is its role in pathogenesis?

Answer 20

The mutation is associated with PAPA syndrome, which leads to decreased inhibition of the inflammasome and increased production of IL-1β and IL-18, driving inflammation.

Question 21

What hormonal influence might be involved in a patient with Pyoderma Gangrenosum reporting premenstrual flares?

Answer 21

Hormonal influences, such as elevated IL-17 and TNF-α, may be involved. Management could include combined oral contraceptives and antiandrogens.

Question 22

What major diagnostic criteria must be fulfilled for Pyoderma Gangrenosum?

Answer 22

The major criteria include the sudden onset of a painful lesion with characteristic morphology and histopathologic exclusion of vasculitis, malignancy, and infection.

Question 23

What minor diagnostic criterion does rapid ulcer healing with systemic corticosteroids fulfill in Pyoderma Gangrenosum?

Answer 23

This fulfills the minor criterion of rapid reduction of pain and inflammation and a 50% decrease in ulcer size within one month of high-dose systemic corticosteroid therapy.

Question 24

What role do neutrophils play in the pathophysiology of Pyoderma Gangrenosum (PG)?

Answer 24

Neutrophils are significant in PG due to:
- Prominent neutrophil-rich dermal infiltrate
- Responsiveness to antineutrophil medications like Dapsone
- Abnormalities in chemotaxis, signaling, and trafficking in patients with PG.

Question 25

How do hormonal influences relate to the occurrence of Pyoderma Gangrenosum (PG)?

Answer 25

Hormonal influences are noted in PG as follows: - Conditions like hidradenitis suppurativa and acne can occur with PG, often linked to premenstrual flares. - A case of PG was managed with a combined oral contraceptive and antiandrogen. - Elevated levels of IL-17 and TNF-α are found in lesional skin of patients with PG, hidradenitis suppurativa, and acne, showing a positive response to TNF-α inhibitors.

Question 26

What are the minor criteria that support the diagnosis of Pyoderma Gangrenosum (PG)?

Answer 26

The minor criteria that support the diagnosis of PG include: 1. Occurrence in an individual with systemic disease as previously described. 2. Classic histologic findings of PG. 3. Rapid reduction of pain and inflammation upon initiation of high-dose systemic corticosteroid therapy, with a 50% decrease in ulcer size within 1 month.

Question 27

What are the histopathologic studies used in the diagnosis of pyoderma gangrenosum (PG)?

Answer 27

Histopathologic studies for PG include: - Incisional wedge skin biopsy from the edge of the PG lesion with normal skin. - 4mm punch biopsies if incisional biopsy is not possible. - Bacterial culture, mycobacterial culture with smear, and fungal culture with microscopy. - Histologic evaluation with H & E preparation and stains like PAS, Giemsa, Fite, and Gran.

Question 28

What laboratory tests are recommended for patients suspected of having pyoderma gangrenosum?

Answer 28

Recommended laboratory tests include: - CBC with differential count - Complete metabolic panel - ESR - Autoantibody screen (ANA, anti-Ro/La antibodies) - Rheumatoid factor - Antiphospholipid antibody screen - Antineutrophilic cytoplasmic antibodies - Serum protein electrophoresis and immunofixation studies - Chest x-ray

Question 29

What are the key components of wound care for pyoderma gangrenosum?

Answer 29

Key components of wound care include: 1. Cleansing daily with tepid sterile saline or a mild antiseptic solution. 2. Applying Silver sulfadiazine 1% cream to facilitate granulation tissue formation and inhibit bacterial growth. 3. Using nonadhesive dressings held in place with a crepe elasticized bandage. 4. Utilizing hydrocolloid dressings that can be left on for 2-3 days. 5. Directed antibiotic therapy based on culture is only required if there are clinical signs of incipient cellulitis.

Question 30

What precautions should be taken for patients with a history of pyoderma gangrenosum during surgical procedures?

Answer 30

Patients with a history of pyoderma gangrenosum should: - Avoid trauma to the skin due to the pathergy phenomenon. - Have close supervision by a dermatologist if surgery is necessary. - Consider a course of systemic steroids during and for at least 2 weeks postoperatively to prevent new PG lesions. - Use subcuticular sutures where possible to minimize trauma.

Question 31

What diagnostic criterion does a history of trauma-induced lesion flaring fulfill in a patient with Pyoderma Gangrenosum?

Answer 31

This fulfills the minor criterion of a history suggestive of pathergy or clinical findings of cribriform scarring.

Question 32

What tests should be included for laboratory testing in a patient with Pyoderma Gangrenosum?

Answer 32

Tests include CBC with differential, complete metabolic panel, ESR, autoantibody screen, rheumatoid factor, antiphospholipid antibody screen, and antineutrophilic cytoplasmic antibodies.

Question 33

What is the purpose of venous reflux studies and an ankle/toe brachial index in a patient with Pyoderma Gangrenosum?

Answer 33

These studies help exclude significant vascular stasis or occlusion as a cause of the skin manifestations.

Question 34

What dressing options are recommended for a patient undergoing wound care for Pyoderma Gangrenosum?

Answer 34

Recommended dressings include nonadhesive dressings held with crepe elasticized bandages and hydrocolloid dressings, which can be left on for 2-3 days.

Question 35

What advanced wound care options are available for a patient with Pyoderma Gangrenosum who has incomplete re-epithelialization?

Answer 35

Options include advanced wound care treatments such as skin substitutes or bioengineered skin products.

Question 36

What is the purpose of vascular studies in skin manifestations?

Answer 36

These studies help exclude significant vascular stasis or occlusion as a cause of the skin manifestations.

Question 37

What dressing options are recommended for a patient with Pyoderma Gangrenosum undergoing wound care?

Answer 37

Recommended dressings include nonadhesive dressings held with crepe elasticized bandages and hydrocolloid dressings, which can be left on for 2-3 days.

Question 38

What advanced wound care options are available for a patient with Pyoderma Gangrenosum with incomplete re-epithelialization?

Answer 38

Options include cultured tissue allografts/autografts and the use of bovine collagen matrix.

Question 39

What precautions should be taken for a patient with a history of Pyoderma Gangrenosum scheduled for surgery?

Answer 39

Precautions include close supervision by a dermatologist, possible systemic steroids during and after surgery, and the use of subcuticular sutures.

Question 40

What histopathologic findings are supportive of the diagnosis of Pyoderma Gangrenosum?

Answer 40

Supportive findings include neutrophil-rich dermal infiltrate, absence of significant vasculitis, and exclusion of infection or malignancy.

Question 41

What histopathologic studies are considered highly suggestive for diagnosing Pyoderma Gangrenosum (PG)?

Answer 41

Histopathologic studies for PG include: - Incisional wedge skin biopsy from the edge of the PG lesion, including normal skin and active inflammation. - If incisional biopsy is not possible, 4mm punch biopsies may be performed. - Sections for bacterial culture, mycobacterial culture, and fungal culture with microscopy. - Histologic evaluation with H & E preparation, along with stains like PAS, Giemsa, Fite, and Gran.

Question 42

What laboratory tests are essential in the evaluation of a patient suspected of having Pyoderma Gangrenosum?

Answer 42

Essential laboratory tests for evaluating Pyoderma Gangrenosum include: - CBC with differential count - Complete metabolic panel - ESR - Autoantibody screen (ANA, anti-Ro/La antibodies) - Rheumatoid factor - Antiphospholipid antibody screen - Antineutrophilic cytoplasmic antibodies - Serum protein electrophoresis and immunofixation studies - Chest X-ray

Question 43

What are the recommended wound care practices for patients with Pyoderma Gangrenosum?

Answer 43

Recommended wound care practices for Pyoderma Gangrenosum include: 1. Cleansing the wound daily with tepid sterile saline or a mild antiseptic solution. 2. Applying Silver sulfadiazine 1% cream to soothe and facilitate granulation tissue formation while inhibiting bacterial growth. 3. Using a nonadhesive dressing held in place with a crepe elasticized bandage, wrapped firmly but not tightly. 4. Utilizing hydrocolloid dressings, which can be left on for 2-3 days. 5. Directed antibiotic therapy based on culture is only required if there are clinical signs of incipient cellulitis around the wound.

Question 44

What precautions should be taken for patients with a history of Pyoderma Gangrenosum undergoing surgery?

Answer 44

Patients with a history of Pyoderma Gangrenosum should take the following precautions when undergoing surgery: - Avoid trauma to the skin due to the pathergy phenomenon. - Have close supervision by a dermatologist during the procedure. - Consider a course of systemic steroids during and for at least 2 weeks postoperatively to prevent the development of new PG lesions. - Use subcuticular sutures where possible to minimize trauma to the skin.

Question 45

What is the hallmark histopathological finding in subcorneal pustular dermatosis?

Answer 45

The hallmark finding is strictly subcorneal pustules filled with polymorphonuclear neutrophils (PMNs) with only occasional eosinophils.

Question 46

What are the common clinical findings associated with subcorneal pustular dermatosis?

Answer 46

Common clinical findings include: 1. Small, discrete, flaccid pustules or vesicles that rapidly turn pustular. 2. Lesions arise in crops on clinically normal or slightly erythematous skin. 3. Pus accumulates in the lower half of the pustule. 4. Lesions may coalesce to form annular or serpiginous patterns. 5. Rupture leads to thin, superficial scales and crusts resembling impetigo. 6. Peripheral spreading with central healing, leaving erythematous areas. 7. No atrophy or scarring, but may leave brownish hyperpigmentation.

Question 47

What are the sites of predilection for subcorneal pustular dermatosis?

Answer 47

The sites of predilection include: - Axilla - Groin - Abdomen - Submammary areas - Flexor aspects of the limbs Rarely affected areas include the face, palms, and soles, while the scalp and mucous membranes are invariant sites.

Question 48

What is the prognosis for patients with subcorneal pustular dermatosis?

Answer 48

The prognosis is generally benign. Without treatment, attacks can recur over many years with variable remissions lasting from a few days to several weeks. Overall, general health is not usually impaired.

Question 49

What are some diseases associated with subcorneal pustular dermatosis?

Answer 49

Associated diseases include: - IgA paraproteinemia - IgA multiple myeloma - Pyoderma gangrenosum - Ulcerative colitis - Crohn disease - CD30+ anaplastic large cell lymphoma - Small cell lung cancer - Rheumatoid arthritis - Systemic lupus erythematosus (SLE) - Hyperthyroidism - Mycoplasma pneumoniae infection - Coccidioides immitis infection.

Question 50

What is the typical histopathologic finding in the dermis for a patient with Subcorneal Pustular Dermatosis?

Answer 50

The dermis contains a perivascular infiltrate of neutrophils, with occasional mononuclear cells and eosinophils.

Question 51

What is the typical histopathologic finding in the epidermis for a patient with Subcorneal Pustular Dermatosis?

Answer 51

The epidermis shows subcorneal pustules with little pathology in the underlying layers, except for migrating leukocytes.

Question 52

What is the likely diagnosis for a patient with small, flaccid pustules that coalesce into annular patterns, and what histopathologic hallmark supports it?

Answer 52

The likely diagnosis is Subcorneal Pustular Dermatosis (SPD). The histopathologic hallmark is strictly subcorneal pustules filled with neutrophils.

Question 53

What is the significance of IgA paraproteinemia in a patient with Subcorneal Pustular Dermatosis?

Answer 53

IgA paraproteinemia is associated with SPD and may reflect a common pathogenic mechanism involving immunologic factors.

Question 54

What is the clinical course of Subcorneal Pustular Dermatosis?

Answer 54

The clinical course involves variable intervals of quiescence followed by sudden development of new lesions, with no atrophy or scarring.

Question 55

What is the diagnosis for a patient with Subcorneal Pustular Dermatosis who has negative DIF but circulating IgA antibodies against desmocollin 1?

Answer 55

The diagnosis is SPD-type IgA pemphigus.

Question 56

What are the common sites of predilection for Subcorneal Pustular Dermatosis?

Answer 56

Common sites include the axilla, groin, abdomen, submammary areas, and flexor aspects of the limbs.

Question 57

What does the absence of systemic symptoms indicate about the severity of Subcorneal Pustular Dermatosis?

Answer 57

The absence of systemic symptoms indicates that SPD is generally a benign condition with no impairment of general health.

Question 58

What is the significance of serpiginous patterns in a patient with Subcorneal Pustular Dermatosis?

Answer 58

The serpiginous pattern is characteristic of SPD and helps differentiate it from other pustular conditions.

Question 59

What is the relationship between Subcorneal Pustular Dermatosis and Crohn's disease?

Answer 59

SPD is associated with Crohn's disease, and both conditions may share a common pathogenic mechanism.

Question 60

What cells are typically found in the perivascular dermal infiltrate of a patient with Subcorneal Pustular Dermatosis?

Answer 60

The infiltrate typically contains neutrophils, with occasional mononuclear cells and eosinophils.

Question 61

What differentiates Subcorneal Pustular Dermatosis from bacterial impetigo?

Answer 61

SPD is differentiated by its histopathologic hallmark of subcorneal pustules filled with neutrophils and the absence of bacterial growth on cultures.

Question 62

What is the typical distribution of lesions in Subcorneal Pustular Dermatosis?

Answer 62

Lesions typically occur symmetrically on the axilla, groin, abdomen, submammary areas, and flexor aspects of the limbs.

Question 63

What is the prognosis for a patient with Subcorneal Pustular Dermatosis who has pustules that leave brownish hyperpigmentation?

Answer 63

The prognosis is generally benign, with attacks recurring over many years but no systemic health impairment.

Question 64

What is the differential diagnosis for a patient with Subcorneal Pustular Dermatosis who has pustules that coalesce into annular patterns?

Answer 64

The differential diagnosis includes bacterial impetigo, dermatitis herpetiformis, pemphigus vulgaris, pemphigus foliaceus, and pustular psoriasis.

Question 65

What is the typical histopathologic finding in lesions of Subcorneal Pustular Dermatosis that have ruptured and formed superficial scales?

Answer 65

The typical finding is subcorneal pustules filled with neutrophils, with little evidence of spongiosis or cytolytic damage to epidermal cells.

Question 66

What is the clinical significance of circinate patterns in a patient with Subcorneal Pustular Dermatosis?

Answer 66

Circinate patterns are characteristic of SPD and help in its clinical diagnosis.

Question 67

What is the clinical course of lesions in Subcorneal Pustular Dermatosis that leave erythematous areas with central healing?

Answer 67

The lesions exhibit peripheral spreading with central healing, and new pustules arise as others disappear.

Question 68

What are the rare sites of involvement in Subcorneal Pustular Dermatosis?

Answer 68

Rare sites include the face, palms, soles, scalp, and mucous membranes.

Question 69

What is the hallmark histopathologic feature of Subcorneal Pustular Dermatosis?

Answer 69

The hallmark feature is strictly subcorneal pustules filled with neutrophils.

Question 70

What are the primary clinical findings associated with Subcorneal Pustular Dermatosis?

Answer 70

- Small, discrete, flaccid pustules or vesicles that rapidly turn pustular. - Lesions arise in crops on clinically normal or slightly erythematous skin within hours. - Pus accumulates in the lower half of the pustule. - Lesions may coalesce into annular or serpiginous patterns. - Rupture leads to thin, superficial scales resembling impetigo. - Peripheral spreading with central healing occurs, leaving erythematous areas. - Episodes of quiescence followed by sudden new lesions are common. - Symmetrical occurrence, primarily in axilla, groin, abdomen, and flexor areas.

Question 71

What are the differential diagnoses for Subcorneal Pustular Dermatosis?

Answer 71

| Condition | Description | |-----------|-------------| | Bacterial impetigo | A bacterial skin infection causing red sores. | | Dermatitis herpetiformis | An itchy skin condition linked to gluten sensitivity. | | Pemphigus vulgaris | An autoimmune disorder causing blisters on the skin and mucous membranes. | | Pemphigus foliaceus | A less severe form of pemphigus affecting the skin. | | Subcorneal dermatosis-type IgA pemphigus | A variant of pemphigus with subcorneal pustules. | | Pustular psoriasis | A type of psoriasis characterized by pustules. | | Necrolytic migratory erythema | A skin condition associated with glucagonoma. | | Acute generalized exanthematous pustulosis | A rare drug reaction causing widespread pustules.

Question 72

What are the treatment options for Subcorneal Pustular Dermatosis?

Answer 72

| Treatment Option | Dosage/Notes | |-----------------|--------------| | **First line**: Dapsone | 50-150 mg/day as required. | | **Second line** (anecdotally reported benefits): | - Retinoids - Photochemotherapy - Colchicine - Cyclosporine - Infliximab - Etanercept