Background
Kyrle disease is a perforating skin condition characterized by the presence of large keratotic papules distributed widely throughout the body. The papules contain a central keratotic plug, which histologically correlates with keratin and necrotic debris. The disease is most closely associated with diabetes mellitus and renal failure.
Pathophysiology
The pathophysiology of Kyrle disease is unclear. Some believe it is a variant of prurigo nodularis or may represent end-stage excoriations of a folliculitis on the legs in patients with renal failure.
The leading theory is that the disease represents transepidermal elimination of keratin and other cellular material. Carter and Constantine[1, 2] have suggested that in Kyrle disease keratinization focally occurs at the basilar layer of the epidermal, rather than normal proliferation with keratinization higher in the epidermis. This elicits a host inflammatory response, resulting in keratin, cellular material, and connective tissue being forced out of the skin through the epidermis.[3] Alteration of dermal connective tissue may also be an initiating step, causing an inflammatory response. Other skin diseases with altered connective tissue have a similar type of inflammatory response, such as elastosis perforans serpiginosa, and perforating collagenosis.
Some literature suggests that Kyrle disease may be a recessively inherited genodermatosis.
Epidemiology
Frequency
In the United States and internationally, Kyrle disease is rare, except in the setting of chronic renal failure. In patients with chronic renal failure, perforating dermatoses (that are closely related to and probably represent variants of Kyrle disease) are more common. Kyrle Disease occurs in 10% of dialysis patients.[4, 5]
Race
Kyrle disease appears to be more common in African Americans, perhaps related to the high incidence of diabetes mellitus and renal failure in this population.
Sex
This disorder may be more common in women.
Age
A wide age range exists among patients with Kyrle disease. The average age at time of presentation is 30 years.
Prognosis
Improvement of skin lesions is possible. The ultimate prognosis depends upon the nature of any underlying systemic disease. Morbidity results from the appearance of the lesions and the intense itching that often is associated with the condition. However, significant morbidity and mortality may be more directly associated with the underlying disease (eg, diabetes mellitus, chronic renal failure, hepatic abnormalities).
History
Lesions may be asymptomatic, but tenderness and especially pruritus are frequently reported. The eruption is chronic, but has been reported to clear following improvement of the underlying related systemic disease (eg, diabetes mellitus, renal failure).
Physical Examination
The primary lesion is a small papule with silvery scale. This eventually enlarges to form a red-brown papule or nodule with a central keratin plug. Some, but not all, of the lesions appear to be follicular. These may coalesce to form larger keratotic plaques. Koebnerization is not ordinarily described as such, but a striking linearity of lesions sometimes is noted. The papules, nodules, and plaques of Kyrle disease tend to occur primarily on the legs, but also develop on the arms and in the head and neck region. Involvement of palms and soles is rare. Ocular changes, including keratotic lesions of conjunctiva and cornea, have been described in a single case report.[11] Note the image below.
View Image | A typical lesion of Kyrle disease with central keratotic crater. |
Causes
As described above, debate about the precise pathophysiology of the disease exists. Some cases appear to be idiopathic or inherited, but other examples of Kyrle disease are associated with systemic disorders. A case report by Kasiakou et al[6] noted regression of lesions following antimicrobial therapy, suggesting a role for bacterial infection in pathogenesis. The following list includes several of the associated systemic disorders:
Diabetes mellitus[7]
Hepatic abnormalities (primary sclerosing cholangitis,[8] alcoholic cirrhosis)[9]
Congestive heart failure
Renal disease - Chronic renal failure, albuminuria, elevated serum creatinine level, abnormal creatinine clearance, polyuria[10]
Laboratory Studies
Examine blood glucose to evaluate for possible diabetes mellitus. Liver function studies are necessary in order to evaluate for possible underlying liver disease (eg, alcoholic cirrhosis). Perform renal function studies, including urinalysis, serum creatinine, and creatinine clearance, in order to evaluate for possible underlying renal disease.
Histologic Findings
A partially parakeratotic plug, which fills an epidermal depression, is present. It may or may not involve a hair follicle. Marked acanthosis of surrounding epithelium usually is present. Within the plug, admixed basophilic debris often is present. Keratinous material extends focally from the basilar layer and may contact the dermis. At this point, necrotic cellular material and degenerated connective tissue are noted to undergo transepidermal elimination. A surrounding mixed infiltrate usually is present, including neutrophils, lymphocytes, and epithelioid histiocytes (macrophages).
Medical Care
Kyrle disease perhaps is most important as a cutaneous sign of a systemic disorder, although idiopathic cases without associated systemic disease occur. Therefore, direct therapeutic efforts toward any underlying condition. For patients in whom itching is a major problem, soothing antipruritic lotions containing menthol and camphor may be helpful. Sedating antihistamines such as hydroxyzine may be helpful for pruritus, especially at night. Potent topical corticosteroids such as topical steroids may help coexisting prurigo nodularis and lichen simplex chronicus.
UV light therapy is considered by some authorities to be the most effective treatment for acquired perforating dermatosis and is particularly helpful for patients with widespread lesions or coexisting pruritus from renal or hepatic disease.
Surgical Care
Carbon dioxide laser or cryosurgery may be helpful for limited lesions. Caution must be exercised for individuals with dark skin, especially with cryosurgery, because of resulting dyspigmentation. Also, lesions on the lower legs, particularly in patients with diabetes mellitus or poor circulation may heal poorly.
Consultations
Dermatologist or internal medicine specialist consultation may be necessary.
Medication Summary
Kyrle disease is relatively rare, so controlled therapeutic studies do not exist. Many treatments have been used, but most have been unsuccessful, including keratolytics, 5-fluorouracil, topical corticosteroids, methotrexate, mercury, chloroquine, and prednisone. One case showed a response to clindamycin therapy.[6] In addition, improvement has been reported with oral vitamin A at a dose of 100,000 IU/day, with or without vitamin E at 400 IU/d, after 1 month of therapy. Topical retinoic acid 0.1% cream also can produce improvement, and changes in lesions have been observed as rapidly as within 6-7 days.
Oral isotretinoin at 40 mg bid (1 mg/kg/day) resulted in decreased pruritus, desiccation, and slough of lesions within 4 weeks, with resurfacing of skin approaching normal within 5 weeks. This drug then was decreased to 40 mg/80 mg on alternate days (0.75 mg/kg/day) for 8 more weeks and discontinued, for a total treatment course of 13 weeks.[13] Etretinate in high doses may also be effective, but relapse has been reported following discontinuation of therapy.
Vitamin A (Aquasol A, A-25)
Clinical Context:
Vitamin A may improve abnormal keratinization.
Class Summary
Fat-soluble vitamins are essential for normal DNA synthesis.
Tretinoin topical (Avita, Renova, Atralin, Retin-A)
Clinical Context:
Topical tretinoin inhibits microcomedo formation and eliminates lesions present. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. It is available as 0.025, 0.05, and 0.1% creams and as 0.01 and 0.025% gels.
Isotretinoin (Amnesteem, Claravis, Myorisan, Sotret)
Clinical Context:
Isotretinoin is an oral agent that treats serious dermatologic conditions. It is a synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A. Isotretinoin decreases sebaceous gland size and sebum production. It may inhibit sebaceous gland differentiation and abnormal keratinization.
The dose used is the standard antiacne dose recommended also for treatment of Kyrle disease in one study; doses and duration of therapy have not been subjected to controlled study, but one study recommended a total duration of 13 weeks, with a reduction of the dose in mid course.
Class Summary
These agents can influence and alter abnormal keratinization.
Author
Mary Piazza Maiberger, MD, Assistant Professor of Dermatology, Howard University College of Medicine; Assistant Clinical Professor of Dermatology, George Washington University School of Medicine and Health Sciences; Chief of Dermatology and Residency Program Site Director, Washington DC VA Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.
Additional Contributors
Daniel J Hogan, MD, Clinical Professor of Internal Medicine (Dermatology), Nova Southeastern University College of Osteopathic Medicine; Investigator, Hill Top Research, Florida Research Center
Disclosure: Nothing to disclose.
Joshua A Zeichner, MD, Assistant Professor, Director of Cosmetic and Clinical Research, Mount Sinai School of Medicine; Chief of Dermatology, Institute for Family Health at North General
Disclosure: Received consulting fee from Valeant for consulting; Received grant/research funds from Medicis for other; Received consulting fee from Galderma for consulting; Received consulting fee from Promius for consulting; Received consulting fee from Pharmaderm for consulting; Received consulting fee from Onset for consulting.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, James W. Patterson, MD, to the development and writing of this article.
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