Kyrle Disease

Article Author:
Ashley Rice
Article Editor:
Daniel Zedek
Updated:
10/27/2018 12:31:40 PM
PubMed Link:
Kyrle Disease

Introduction

Kyrle Disease is a rare skin condition classified as a subtype of acquired perforating dermatosis, along with reactive perforating collagenosis, elastosis perforans serpinginosa and perforating folliculitis.[1] It was first described in 1916 by Austrian pathologist and dermatologist Josef Kyrle in a diabetic woman with generalized hyperkeratotic papules and was originally coined "hyperkeratosis follicularis et parafollicularis in cutem penetrams."[1][2] Due to significant clinical overlap, follicular and non-follicular morphology, and variations in histology with differing disease stages, acquired perforating dermatosis was proposed as an umbrella term for all adult-onset perforating disorders. However, there is controversy in the literature as to the classification of Kyrle disease. While some authors use Kyrle disease interchangeably with acquired perforating dermatosis, others define it as a variant of prurigo nodularis that represents end-stage excoriated folliculitis.[3]

Kyrle disease most commonly manifests as multiple, discrete, eruptive papules with a central keratotic plug on the lower extremities. On histopathology, there is a characteristic transepidermal elimination of abnormal keratin.[1][3] The exact etiology of Kyrle disease has not been elucidated. The majority of case reports suggest it occurs secondary to chronic systemic diseases, most commonly renal failure (stages 4 and 5) and diabetes mellitus. Meanwhile, evidence of Kyrle disease as a primary perforating disorder has been seen in small case reports that show a genetic predisposition. Treatment can be difficult and typically focuses on management of underlying medical conditions. Keratolytic agents are also recommended as first-line therapy.[1][3]

Etiology

The exact etiology of Kyrle disease is unknown. Many theories have been proposed in the literature including infectious, abnormal keratinization, defective differentiation of the epidermis and dermoepidermal junction, elevated serum and tissue concentrations of fibronectin, uremia (renal failure), and hyperphosphatemia (diabetes mellitus). The high incidence of systemic disease associated with the development of Kyrle disease suggests an underlying systemic disorder as the main etiology.[1][3]

Small case reports have shown a possible genetic predisposition with discoveries of both autosomal dominant and autosomal recessive inheritance patterns. However, familial predisposition has not been extensively studied, and future studies are warranted to determine genomic significance.[1][3]

Epidemiology

Kyrle disease typically occurs during adulthood between the age of 30 and 50 years. There is a higher incidence in females with a female-to-male ratio of up to 6:1.[1]

Kyrle disease is most commonly associated with chronic renal disease and diabetes mellitus, particularly in those with associated diabetic nephropathy. It is estimated that 10% of hemodialysis patients will eventually develop Kyrle disease.[1][4] In rare cases, it has been seen in tuberculosis, pulmonary aspergillosis, scabies, atopic dermatitis, AIDS, neurodermatitis, malignancy, hepatic disorders, congestive heart failure, and endocrinological disorders.[1]

Pathophysiology

In the setting of systemic disease, it is postulated that various metabolic derangements underlie the pathophysiology of Kyrle disease. The fact that Kyrle disease also occurs in non-diabetic renal diseases suggests uremia, rather than hyperglycemia, as the causative factor in diabetic and renal failure patients.[3] In patients with diabetic nephropathy, Joseph et al. [4] found that the only consistent abnormality was hyperphosphatemia, suggesting a role in the pathogenesis. It is theorized that excess urea and/or phosphate is deposited in the dermis with subsequent extrusion of the material through epidermal follicular openings and the formation of perforating canals.[4]

In addition, serum and immunohistochemical studies have shown an increase in fibronectin levels and deposition, which may play a role in inciting epithelial migration and proliferation, leading to perforation.[1][5] Others have suggested that advanced glycosylation end products and oxidized low-density lipoproteins lead to abnormal keratinization, defective differentiation of the epidermis and dermo-epidermal junction, and vasculopathy. This causes a cutaneous response in the form of transdermal elimination.[1][6] Lastly, a single case report proposed the role of anaerobic bacteria in the pathogenesis of Kyrle disease based on the regression of skin lesions with clindamycin.[1][7]

Histopathology

Kyrle disease is characterized by transdermal elimination of keratotic material with no collagen or elastic fibers. This differentiates Kyrle disease from other acquired perforating disorders that exhibit transdermal elimination of collagen and elastic fibers. These include reactive perforating collagenosis, elastosis perforans serpinginosa and perforating folliculitis. In addition, there is an overlying keratotic plug in an atrophic-appearing epidermis. A foreign body granulomatous reaction composed of dermal histiocytic and lymphocytic infiltrates may be present. Orthokeratosis, parakeratosis, and abnormal keratinization may also be observed.[1]

History and Physical

Kyrle disease typically presents as hyperkeratotic papules and nodules with a central keratotic plug. Skin lesions occur most commonly on the lower extremities, especially the calf, tibial region, and posterior aspect. It may also affect the arms and head and neck regions. Rarely, there is involvement of the palms and soles.[1] Koebnerization, in which skin lesions form at sites of injury, has also been reported.[1][8]

Evaluation

Kyrle disease is diagnosed based on characteristic clinical and histopathologic findings. Patients should have close clinical follow-up of any underlying systemic diseases by their primary care physician and other corresponding specialty physicians.

Treatment / Management

To date, there are no well-designed randomized control trials studying treatment therapies for Kyrle disease. Treatment recommendations are currently based on anecdotal reports or small case series. Keratolytics such as salicylic acid or urea are considered first-line therapy. Emollients and oral antihistamines have been used to relieve pruritus. Electrocautery, cryotherapy, CO2 laser, topical retinoids, isotretinoin, and psoralen plus ultraviolet A radiation are alternative therapies. Oral clindamycin 300 mg three 3 a day for one month has also shown beneficial results.[1] Discontinuation of these therapies often results in recurrence of skin lesions[1][9], although there have been reports of complete regression after renal transplantation in dialysis patients.[10] Surgical excision is reserved for severe, refractory cases.[1]

Differential Diagnosis

Kyrle disease must be differentiated from other disorders that cause papular or nodular eruptions with hyperkeratotic central plugs. These include the following:

  • Prurigo nodularis (some authors argue Kyrle disease is a variant of prurigo nodularis)[3]
  • Multiple keratoacanthomas (can also mimic Kyrle disease histologically)
  • Excoriated lesions (prurigo simplex)
  • Folliculitis
  • Arthropod hypersensitivity reaction
  • Perforation of exogenous or endogenous foreign material
  • Dermatofibromas

If koebnerization occurs, more linearly distributed lesions should be included in the differential. These include the following:

  • Psoriasis
  • Lichen planus
  • Verrucae

Diagnosis can be difficult as patients with acquired perforating disorders often have co-existing folliculitis and prurigo nodularis.[3] In addition, histology may represent various lesions at different stages. Patients who have a history of diabetes mellitus with concomitant renal disease or those on hemodialysis are more likely to have an acquired perforating disease.

Enhancing Healthcare Team Outcomes

Kyrle disease commonly presents in patients with significant comorbidities such as end-stage renal disease and diabetes mellitus. Thus, it is imperative that dermatologists have a high index of suspicion for renal failure and/or diabetes mellitus or potential worsening of these disorders in patients presenting with Kyrle disease. Dermatologists must work closely with primary care physicians and other specialty physicians, such as nephrologists or endocrinologists, to prevent a negative impact on patients’ quality of life. Future studies on the morbidity and mortality of Kyrle disease are still needed as the current literature is based on small case series. (Level V)