Kyrle's Disease (hyperkeratosis follicularis et parafollicularis in cutem penetrans)
Are You Confident of the Diagnosis?
What you should be alert for in the history
A history of diabetes, renal or hepatic disease, and congestive heart failure have been reported as associations with Kyrle's disease. Up to 10% of renal dialysis patients develop Kyrle's disease. However, other authors deny any such systemic associations. Curiously, Kyrle's original patient, reported in 1916, was a 22-year-old non-diabetic woman who developed diabetes 8 years later.
Characteristic findings on physical examination
The following is a discussion of Kyrle's disease as it is classically defined in the older medical literature. There is still considerable controversy in the literature regarding the nosologic position of Kyrle's disease, as the criteria for its diagnosis are not generally agreed upon. Some authors consider it to be a distinct disorder of keratinization, while most believe Kyrle's disease falls under the inclusive category of acquired perforating dermatoses.
Clinically, the lesions of Kyrle's disease are described as chronic, scattered, generalized, non-pruritic papules with cone-shaped hyperkeratotic plugs (
Multiple hyperpigmented hyperkeratotic papules and plaques on the extremities.
The disease itself is reported as asymptomatic, but may be associated with tenderness or pruritus, particularly after the lesions have been traumatized. Duration of cutaneous eruption has ranged from 4 months to 43 years but generally runs an extremely chronic course, lasting decades. There is no sexual or racial predilection.
Expected results of diagnostic studies
The main histologic features as defined by some authors are:
1. A keratotic plug that fills an epidermal invagination
2. Parakeratosis present in parts of the plug
3. A focus of vacuolated dyskeratotic cells that extends to the basal cell layer and eventually penetrates into the dermis, inducing an inflammatory and granulomatous reaction.
Although initially the plug contained primarily keratin, retrospective studies have identified both collagen and elastin fibers, albeit in relatively smaller proportions than those found in reactive perforating collagenosis (RPC) or elastosis perforans serpiginosa (EPS).
The principal clinical and histological differential diagnostic considerations include EPS, RPC, and perforating folliculitis (PF). Clinical considerations include lichen planus, prurigo nodularis, eruptive keratoacanthomas of Grzybowski, Darier disease, keratosis pilaris, Flegel disease, and phrynoderma of hypovitaminosis A.
Who is at Risk for Developing this Disease?
Given the difficulty defining authentic cases of Kyrle's disease, true associations are difficult to confirm or refute. Patients with the following systemic disorders are at increased risk of developing Kyrle's disease:
Hepatic abnormalities (primary sclerosing cholangitis, alcoholic cirrhosis)
Congestive heart failure
Renal disease - Chronic renal failure, albuminuria, elevated serum creatinine level, abnormal creatinine clearance, polyuria. Kyrle's disease appears to be more common in patients on hemodialysis.
What is the Cause of the Disease?
The etiology of Kyrle's disease is unknown. It has been described in successive generations and siblings, suggesting a genetic predisposition, however the exact mode of inheritance remains controversial.
The basic pathogenic event appears to be an uncoupling of epidermal proliferation and differentiation such that the keratinization occurs faster than production of new cells. The hyperkeratotic plug later perforates into the dermis, inducing a granulomatous reaction. Thus, rather than material being transepidermally eliminated, the primary pathologic process here is that of hyperkeratotic material penetrating (outside in).
Since the site of Kyrle's disease may be follicular, many of the reported cases may have been perforating folliculitis, while others have been variably reclassified as RPC or EPS. Therefore, it has been suggested that Kyrle's disease is the same disorder as acquired perforating dermatosis (APD).
Systemic Implications and Complications
The notorious difficulty in distinguishing Kyrle's disease from APD makes an evaluation of its association with diabetes or renal disease difficult.
- Topical keratolytics
- Topical corticosteroids
- Topical retinoids
- Intralesional mercury - Systemic methotrexate
- Systemic prednisone
- Systemic retinoids
- CO2 laser surgery
- Ultraviolet type B (UVB) phototherapy (broad and narrow band)
There is no known specific therapy for Kyrle's disease.
Unsuccessful therapies have included topical keratolytics, topical corticosteroids, 5-fluorouracil, and mercury injections. Topical retinoic acid 0.1% cream has produced flattening of the lesions as soon as one week after starting therapy. Systemic methotrexate, prednisone, and vitamin A at 100,000U/day have all been reported, with inconsistent efficacy. Kyrle treated his own patient with curettage and UVB phototherapy; however, lesions tended to recur after a short remission.
Physical modalities such as electrocautery, cryotherapy, and CO2 laser surgery are only temporarily effective.
UVB phototherapy is considered by some authorities to be the most effective treatment for Kyrle's disease and is particularly helpful for patients with widespread lesions or coexisting pruritus from renal or hepatic disease. A regimen of three weekly treatments for 6 weeks should be tried before treatment could be declared ineffective.
Optimal Therapeutic Approach for this Disease
An optimal treatment approach has not been defined for Kyrle's Disease because of the difficulty in defining Kyrle's disease as a unique clinical entity, and the subsequent absence of evidence regarding therapy. If a case of Kyrle's disease is suspected, it would be reasonable to take the same therapeutic approach as for APD (see separate chapter).
In patients with renal disease, treatment of underlying disease or renal transplantation may result in improvement of cutaneous disease. If unrelated to renal disease or if stabilization of renal disease is ineffective, first-line therapy is topical retinoids and broadband or narrowband UVB or psoralen and ultraviolet light (PUVA) phototherapy. Phototherapy is particularly beneficial in patients with considerable pruritus, as it helps to relieve symptoms. Anecdotally, change in dialysis tubing has been reported to improve the condition in a number of patients on hemodialysis.
The first step in management is to exclude diabetes and renal failure. General measures include trauma avoidance, trimming of fingernails, wearing gloves to minimize trauma from scratching, behavior modification, and transcutaneous nerve stimulation.
Renal transplantation, if possible, can potentially cure cutaneous disease.
Patients need to be educated that the disease is likely to follow a chronic course and that local measures, while effective in certain patients, are unlikely to result in complete clearance of lesions. (See chapter on perforating dermatoses.)
Unusual Clinical Scenarios to Consider in Patient Management
Hereditary cases of Kyrle's disease have been reported and suggest an autosomal-resessive mode of transmission. Isolated case reports of Kyrle's disease involving buccal mucosa and conjunctiva also exist in the literature.
What is the Evidence?
Rapini, RP, Herbert, AA, Drucker, CR. "Acquired perforating dermatosis. Evidence for combined transepidermal elimination of both collagen and elastic fibers". Arch Dermatol. vol. 125. 1989. pp. 1074-8.(This study reports on four patients with renal disease and/or diabetes whose skin biopsy specimens revealed both collagen and elastic fibers undergoing transepidermal elimination, thus providing convincing evidence for the concept of acquired perforating dermatosis.)
Kahana, M, Trau, H, Dolev, E, Schewach-Millet, M, Gilon, E. " Perforating folliculitis in association with primary sclerosing cholangitis". Am J Dermatopathol. vol. 7. 1985. pp. 271-6.(The study reports two patients with primary sclerosing cholangitis who developed perforating skin lesions on the extremities. The course of the eruption paralleled the severity of the biliary disease.)
Salomon, RJ, Baden, TJ, Gammon, WR. " Kyrle's disease and hepatic insufficiency". Arch Dermatol. vol. 122. 1986. pp. 18-9.(A case report describing an association of Kyrle's disease with hepatic insufficiency)
Saleh, HA, Lloyd, KM, Fatteh, S. " Kyrle's disease effectively treated with isotretinoin". J Fla Med Assoc. vol. 80. 1993. pp. 395-7.(This report describes treatment of a 63-year-old hemodialysis patient with systemic isotretinoin for 13 weeks, which resulted in complete resolution of the cutaneous lesions. The dose of isotretinoin was 40mg twice a day (1mg/kg/day) for the first 5 weeks and 40mg/80mg on alternate days (0.75mg/kg/d) for the remaining 8 weeks.)
Hurwitz, RM, Melton, ME, Creech, FT, Weiss, J, Handt, A. " Perforating folliculitis in association with hemodialysis". Am J Dermatopathol. vol. 4. 1982. pp. 101-8.(A clinicopathologic study describing five patients on hemodialysis for diabetic nephropathy who had developed a perforating dermatosis within 2 months after initiation of hemodialysis.)
Carter, VH, Constantine, VS. " Kyrle's disease. I. ". Arch Dermatol Ju. vol. 97(6). 1968. pp. 624-32.
Constantine, VS, Carter, VH. " Kyrle's disease. II. Histopathologic findings in five cases and review of the literature". Arch Dermatol Jun. vol. 97(6). 1968. pp. 633-9.(The previous two studies are the earlier reports of Kyrle's disease, which include the proposed pathogenic mechanism of transepidermal elimination.)
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