71: Acquired Perforating Disorders Flashcards
What are the primary clinical features of acquired perforating collagenosis/Kyrle disease?
Characterized by round, umbilicated, skin-colored, erythematous or hyperpigmented papules and nodules with a central crust or keratotic plug. Predominant sites include the extensor surfaces of the extremities and the trunk. Less commonly involved areas are the face and scalp. Central keratotic core is the most specific clinical finding. Scratching can lead to Koebnerization with linear umbilicated papules arising in excoriated skin.
What systemic conditions are most commonly associated with adult-onset acquired perforating disorders (APD)?
- Chronic Kidney Disease (CKD)
- Diabetes Mellitus (DM)
- Diabetic nephropathy is the most common cause of CKD among APD patients. Lesions associated with CKD and DM are typically chronic and parallel systemic disease.
What are the four clinicopathologic entities associated with adult-onset nonfamilial/acquired lesions of APD?
- Kyrle Disease (KD)
- Acquired Perforating Collagenosis (APC)
- Perforating Folliculitis
- Acquired Elastosis Perforans Serpiginosa (AEPS)
How does elastosis perforans serpiginosa typically present and what are its characteristics?
Papules in serpiginous configuration, often with central atrophy. Typically localized to one region of the body, such as the neck, trunk, or extremities. Often asymptomatic and may occasionally manifest a Koebnerization response. More common in males than females (4x). Familial inheritance is autosomal dominant (AD).
What is the mode of inheritance for reactive perforating collagenosis and its typical presentation?
Reactive perforating collagenosis is an extremely rare familial disease. It often presents in early childhood. The mode of inheritance can be autosomal dominant (AD) or autosomal recessive (AR). Small keratotic papules develop on the upper and lower extremities and face following trauma, exhibiting the strongest Koebnerization response.
A patient with chronic kidney disease (CKD) presents with umbilicated papules on the extensor surfaces of their extremities. What is the most likely diagnosis, and what systemic condition is this associated with?
The most likely diagnosis is acquired perforating collagenosis (APC) or Kyrle disease (KD). These conditions are commonly associated with chronic kidney disease (CKD) and diabetes mellitus (DM).
A child presents with small keratotic papules on the extremities following trauma. The family history reveals similar conditions. What is the diagnosis, and what is the inheritance pattern?
The diagnosis is reactive perforating collagenosis, an extremely rare familial disease. The inheritance pattern can be autosomal dominant (AD) or autosomal recessive (AR).
A patient with Down syndrome develops papules in a serpiginous configuration on the trunk. What is the diagnosis, and what systemic associations should be considered?
The diagnosis is elastosis perforans serpiginosa (AEPS). Systemic associations include inborn disorders of connective tissue metabolism such as Ehlers-Danlos syndrome, Marfan syndrome, and pseudoxanthoma elasticum.
A patient presents with follicular-based lesions that lack a Koebner response and have a waxing-and-waning course. What is the likely diagnosis, and how does it differ from other APDs?
The likely diagnosis is perforating folliculitis. It differs from other APDs as it exhibits a follicular-based distribution with minimal Koebner response and a waxing-and-waning course.
A patient with a history of trauma develops keratotic papules on the face and extremities. What is the diagnosis, and what is the strongest clinical response observed?
The diagnosis is reactive perforating collagenosis. The strongest clinical response observed is Koebnerization, where linear umbilicated papules arise in excoriated skin.
What are the primary clinical features of acquired perforating collagenosis/Kyrle disease, and how do they differ from elastosis perforans serpiginosa?
Acquired Perforating Collagenosis/Kyrle Disease:
- Characterized by round, umbilicated, skin-colored, erythematous or hyperpigmented papules and nodules with a central keratotic core.
- Predominant sites: extensor surfaces of the extremities and trunk.
- Less commonly involved: face and scalp.
- Scratching can lead to Koebnerization with linear umbilicated papules.
Elastosis Perforans Serpiginosa:
- Papules in serpiginous configuration, often with central atrophy.
- Typically localized to one region of the body (neck, trunk, or extremities).
- Often asymptomatic and may manifest Koebnerization response, with a higher prevalence in males.
Discuss the associations between acquired perforating disorders (APD) and systemic conditions, particularly focusing on chronic kidney disease and diabetes mellitus.
Associations of APD:
1. Chronic Kidney Disease (CKD):
- Most common systemic condition associated with adult-onset APD.
- Diabetic nephropathy is the most common cause of CKD among APD patients.
- Lesions are typically chronic and parallel systemic disease.
- Diabetes Mellitus (DM):
- Commonly associated with APD.
- Follicular-based lesions unassociated with CKD or DM often lack a Koebner response and have a waxing-and-waning course.
Other Associations:
- Prolonged use of tumor necrosis factor-α inhibitors, indinavir, and sorafenib is associated with APD.
- Prolonged D-penicillamine therapy may lead to adverse effects like AEPS.
- Conditions such as Down syndrome and inborn disorders of connective tissue metabolism (e.g., Ehlers-Danlos syndrome) are also associated with APD.
What is the significance of Koebnerization in the context of acquired perforating disorders, and how does it manifest differently in various types of APD?
Koebnerization in Acquired Perforating Disorders (APD):
- Definition: Koebnerization refers to the phenomenon where skin lesions appear at sites of trauma or injury.
- Acquired Perforating Collagenosis/Kyrle Disease:
- Scratching can lead to Koebnerization, resulting in linear umbilicated papules in excoriated skin.
- Elastosis Perforans Serpiginosa:
- May occasionally manifest Koebnerization response, but is often asymptomatic.
- Perforating Folliculitis:
- Exhibits minimal Koebner response, with a follicular-based distribution.
- Reactive Perforating Collagenosis:
- Has the strongest Koebnerization response, often developing small keratotic papules following trauma, particularly in early childhood.
A patient with chronic kidney disease develops lesions with a central keratotic plug. What is the most specific clinical finding, and how does it aid in diagnosis?
The most specific clinical finding is the central keratotic plug, which aids in diagnosing acquired perforating disorders (APDs) such as Kyrle disease (KD) or acquired perforating collagenosis (APC).
A patient with elastosis perforans serpiginosa (AEPS) presents with papules localized to the neck. What is the typical gender distribution, and what inheritance pattern is observed in familial cases?
Males are affected four times more often than females. Familial cases exhibit autosomal dominant (AD) inheritance.
A patient with diabetes mellitus develops lesions with a Koebner response. What is the clinical significance of this response in acquired perforating disorders (APDs)?
The Koebner response, where new lesions develop at sites of trauma, is a hallmark of reactive perforating collagenosis and indicates heightened skin reactivity.
A patient with elastosis perforans serpiginosa (AEPS) presents with papules in a serpiginous configuration. What is the typical clinical course, and what systemic conditions should be evaluated?
The clinical course is often asymptomatic and localized to one region of the body. Systemic conditions to evaluate include inborn disorders of connective tissue metabolism, such as Ehlers-Danlos syndrome and Marfan syndrome.
What are the common associations with Acquired Perforating Dermatosis (APD)?
Common associations with APD include:
- Chronic kidney disease
- Diabetes mellitus (both dependent and non-dependent)
- Scabies
- Rare associations such as AIDS, Atopic dermatitis, and various liver diseases.
What are the four types of perforating folliculitis and APC?
The four types of perforating folliculitis and APC are:
1. APC - collagen bundles are detected within the plug.
2. AEPS - elastic fibers are instead noted.
3. KD - amorphous dermal material with fibrin and/or keratin comprises the extruded contents.
4. Perforating folliculitis - perforation of the follicular epithelium by degenerating collagen and extracellular matrix.
What laboratory tests are recommended for evaluating comorbidities in patients with APD?
Recommended laboratory tests for evaluating comorbidities include:
- Fasting blood glucose
- Glucose tolerance test
- Serum creatinine
- Glomerular filtration rate or creatinine clearance
- Serum uric acid
- Liver function tests
- Thyroid function tests.
What are the complications associated with Acquired Perforating Dermatosis?
Complications associated with Acquired Perforating Dermatosis include:
- Most complications arise from underlying systemic disease.
- Secondary infections.
- ICD/ACD (Inflammatory Cutaneous Disease/Acquired Cutaneous Disease).
- Post-inflammatory pigmentary alteration and scarring.
What management strategies are recommended for patients with chronic kidney disease (CKD) and APD?
Management strategies for CKD patients with APD include:
- Improvement in lesions after changing the type of dialysis tubing.
- Modification of dialysis procedure.
- Renal transplantation.
- Use of retinoids (topical/oral), steroids (topical/oral), and ultraviolet B phototherapy as commonly employed treatments.
- Phototherapy for uremic pruritus.
A patient with a history of prolonged D-penicillamine therapy develops serpiginous papules localized to the neck. What is the likely diagnosis, and what is the pathogenesis?
The likely diagnosis is acquired elastosis perforans serpiginosa (AEPS). Prolonged D-penicillamine therapy alters dermal elastic fibers, leading to ‘bramble bush-appearing’ fibers in the dermis.
A patient with diabetes mellitus presents with chronic lesions that parallel their systemic disease. What type of acquired perforating disorder is most likely, and what is the specific histopathological finding?
The most likely type is Kyrle disease (KD) or acquired reactive perforating collagenosis. Histopathological findings include transepidermal elimination of dermal material through an epidermal invagination.
A patient with chronic renal failure presents with pruritic lesions that improve after renal transplantation. What is the likely diagnosis, and what treatment options are available?
The likely diagnosis is an acquired perforating disorder (APD) associated with chronic kidney disease (CKD). Treatment options include retinoids (topical/oral), steroids (topical/oral), ultraviolet B phototherapy, and renal transplantation.
A patient with diabetes mellitus develops lesions with a central keratotic core. What is the most specific clinical finding, and what is the pathogenesis?
The most specific clinical finding is the central keratotic core. Pathogenesis involves traumatized keratinocytes binding advanced glycation end product-modified collagens via CD36, leading to keratinocyte terminal differentiation and upward movement.
A patient undergoing dialysis develops lesions with extruded collagen. What is the diagnosis, and what histopathological findings support this?
The diagnosis is acquired perforating collagenosis (APC). Histopathological findings include transepidermal elimination of collagen bundles within the plug.
A patient with chronic kidney disease presents with lesions that resolve upon discontinuation of manipulation or trauma. What is the primary inciting factor, and what is the diagnosis?
The primary inciting factor is superficial trauma to the epidermis. The diagnosis is an acquired perforating disorder (APD).
A patient with elastosis perforans serpiginosa (AEPS) presents with enhanced expression of elastin receptors. What is the significance of this finding?
Enhanced expression of elastin receptors in the epidermis surrounding the elastic material plays a role in the pathogenesis of elastosis perforans serpiginosa (AEPS).
A patient with diabetes mellitus develops lesions with focal inflammatory infiltrate in the dermis. What cells predominate in early versus older lesions?
In early lesions, neutrophils predominate. In older lesions, lymphocytes, macrophages, or multinucleated giant cells are present.
A patient with acquired perforating collagenosis (APC) undergoes histopathological examination. What are the key findings in the epidermis and dermis?
Key findings include transepidermal elimination of dermal material through an epidermal invagination, a central keratotic plug with crusting or hyperkeratosis, and focal inflammatory infiltrate in the dermis.
A patient with chronic kidney disease develops lesions with extruded elastic fibers. What is the diagnosis, and what histopathological findings support this?
The diagnosis is acquired elastosis perforans serpiginosa (AEPS). Histopathological findings include transepidermal elimination of elastic fibers.
A patient with acquired perforating disorder (APD) undergoes laboratory evaluation. What tests should be performed to evaluate for comorbidities?
Tests include fasting blood glucose, glucose tolerance test, serum creatinine, glomerular filtration rate or creatinine clearance, serum uric acid, liver function tests, and thyroid function tests.
A patient with elastosis perforans serpiginosa (AEPS) presents with ‘bramble bush-appearing’ fibers in the dermis. What is the likely cause, and what systemic condition is associated?
The likely cause is prolonged D-penicillamine therapy, which alters dermal elastic fibers. This condition is associated with systemic diseases like Wilson’s disease.
A patient with chronic kidney disease develops lesions with amorphous dermal material. What is the diagnosis, and what comprises the extruded contents?
The diagnosis is Kyrle disease (KD). The extruded contents comprise amorphous dermal material with fibrin and/or keratin.
What is the likely cause of elastosis perforans serpiginosa (AEPS) and what systemic condition is associated?
The likely cause is prolonged D-penicillamine therapy, which alters dermal elastic fibers. This condition is associated with systemic diseases like Wilson’s disease.
What is the diagnosis for a patient with chronic kidney disease who develops lesions with amorphous dermal material?
The diagnosis is Kyrle disease (KD). The extruded contents comprise amorphous dermal material with fibrin and/or keratin.
What is the role of fibronectin in the pathogenesis of lesions in diabetes mellitus?
Fibronectin plays a vital role in epithelial cell signaling, migration, and differentiation by linking keratinocytes with Type IV collagen within the basement membrane.
What other molecular imbalances are involved in the pathogenesis of lesions in chronic kidney disease?
Other molecular imbalances include matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1.
What are potential underlying conditions that may predispose a patient to perforating folliculitis and acquired perforating collagenosis (APC)?
Potential underlying conditions include vasculopathy/angiopathy related to diabetes mellitus, microdeposition of exogenous materials within the dermis, metabolic derangements including vitamin A deficiency, and traumatized keratinocytes.
How does superficial trauma to the epidermis act as an inciting factor in acquired perforating dermatosis (APD)?
Superficial trauma to the epidermis can lead to the development of prurigo nodules and resolution of APD lesions upon discontinuation of manipulation or trauma.
What histopathological features are characteristic of perforating folliculitis and APC?
Histopathological features include transepidermal elimination of dermal material, central keratotic plug with crusting or hyperkeratosis, focal inflammatory infiltrate with neutrophils in early lesions, and types of lesions such as collagen bundles in APC and elastic fibers in AEPS.
What laboratory tests are recommended for evaluating comorbidities in patients with acquired perforating dermatosis?
Recommended laboratory tests include fasting blood glucose, glucose tolerance test, serum creatinine, glomerular filtration rate or creatinine clearance, serum uric acid, liver function tests, and thyroid function tests.
What management strategies are effective for patients with acquired perforating dermatosis, particularly those with chronic kidney disease (CKD)?
Effective management strategies include modification of dialysis procedure, renal transplantation for severe cases, topical/oral retinoids and steroids, ultraviolet B phototherapy, and phototherapy for uremic pruritus.
What is the likely diagnosis for a patient with chronic kidney disease who develops lesions that improve after changing the type of dialysis tubing?
The likely diagnosis is an acquired perforating disorder (APD), suggesting that microdeposition of exogenous materials may play a role in the pathogenesis.
What is the diagnosis for a patient with diabetes mellitus who develops lesions with transepidermal elimination of keratin?
The diagnosis is Kyrle disease (KD). Histopathological findings include transepidermal elimination of keratin and amorphous dermal material.
What is the significance of parakeratosis in lesions of a patient with diabetes mellitus?
Parakeratosis indicates abnormal keratinization and is a histopathological feature of acquired perforating disorders (APDs).
What is the composition of the inflammatory infiltrate in early versus older lesions of chronic kidney disease?
In early lesions, the infiltrate is predominantly neutrophilic. In older lesions, it includes lymphocytes, macrophages, or multinucleated giant cells.
What dermal material is detected within the plug in a biopsy of a patient with acquired perforating collagenosis (APC)?
In APC, collagen bundles are detected within the plug, while in AEPS, elastic fibers are noted instead.
What laboratory tests should be performed for a patient with chronic kidney disease who develops lesions with extruded collagen?
Laboratory tests include fasting blood glucose, glucose tolerance test, serum creatinine, glomerular filtration rate or creatinine clearance, serum uric acid, liver function tests, and thyroid function tests.
What is the diagnosis for a patient with chronic kidney disease who develops lesions with amorphous dermal material?
The diagnosis is Kyrle disease (KD), which is most commonly associated with chronic kidney disease (CKD).
What molecular mechanism links keratinocytes to the process of glycated collagen in diabetes mellitus?
Traumatized keratinocytes bind advanced glycation end product-modified collagens via the receptor CD36, inducing keratinocyte terminal differentiation and upward movement.
What is the diagnosis for a patient with chronic kidney disease who develops lesions with extruded elastic fibers?
The diagnosis is acquired elastosis perforans serpiginosa (AEPS). Enhanced expression of elastin receptors in the epidermis plays a role in the pathogenesis.
What are the recommended topical therapies for Acquired Perforating Dermatosis and their respective dosages?
Treatment | Action | Dosage |
|————————|———-|———————————|
| Retinoid acid | Retinoid | 0.025% gel* |
| Tretinoin | Retinoid | 0.1% cream one to three times daily |
| Tazarotene | Retinoid | 0.1% gel daily |
| Beclomethasone | Corticosteroid | 0.1% cream |
| Triamcinolone acetonide| Corticosteroid | 10 mg/mL intralesional injection |
| Imiquimod | Immune response modifier | Daily for 6 weeks then 3 times per week for 4 weeks |
| Phenol | Antipruritic | 0.5% phenol with 10% glycerin in Sorbolene cream* |
| Capsaicin | Topical analgesic | 0.025% or 0.075% ointment |
What systemic therapies are recommended for Acquired Perforating Dermatosis?
Treatment | Action | Dosage |
|————————|———-|———————————|
| Isotretinoin | Retinoid | Isotretinoin 0.5 mg/kg/day* |
| Acitretin | Retinoid | 25-30 mg daily* |
| Prednisone | Corticosteroid | 30 mg daily* |
| Allopurinol | Xanthine oxidase inhibitor | 100 mg daily* |
| Doxycycline | Antibiotic | 100 mg daily* |
| Minocycline | Antibiotic | 500 mg twice daily* |
| Clindamycin | Antibiotic | 300 mg three times daily* |
| Hydroxychloroquine | Antimalarial | 200 mg daily* |
What physical therapies are utilized in the treatment of Acquired Perforating Dermatosis?
Treatment | Action | Dosage |
|————————|———-|———————————|
| UVB | Phototherapy | MED for 2 minutes every other day, 30 seconds for 2-4 weeks* |
| NUVB | Phototherapy | Three times a week for 2 months at 400 mJ/cm², increased to 1,500 mJ/cm², then 1-3 times per week, 10-15 exposures* |
| PUVA | Phototherapy | Four times per week for total of 36.2 J/cm²* |
| Liquid nitrogen | Cryotherapy | 10 seconds, on five occasions over 4 months, one occasion 3 months later* |
| Carbon dioxide laser | Laser | Five lesional passes at 300 J (pattern 5, size 7, density 6), followed by 3 resurfacing passes at 300 J (pattern 2, size 8, density 5), power of 80 W* |
| TENS | Other | 1 hour daily for 3 weeks* |
| Surgical debridement | Other | - |
