Gál A.I.1, Bar-Ilan E.1, Vass V.2, Veres K.1, Szalai Z.1
1Pediatric Dermatology Department, 2Pathology Department
Heim Pál National Children’s Institute, Budapest, Hungary

Keywords: cholangitis, acquired perforating dermatosis, child.

Abbreviations: ANCA = anti-neutrophil cytoplasmic antibodies; APD = acquired perforating dermatosis;
ASC = autoimmune sclerosing cholangitis; KD = Kyrle’s disease; SMA = smooth muscle antibody.

Case report. A 4-year-old healthy girl presented to the Department of Pediatric Dermatology with a persistent pruritic rash that appeared abruptly 3 months prior. Her family medical history was unremarkable. Physical examination revealed mild icterus and yellow sclera in addition to a widespread, symmetrically distributed, unique rash favoring the extremities. The rash was composed of multiple hyperkeratotic, centrally ulcerated papules, plaques and nodules with excoriation (Fig. 1, 2, 3). Initial differential diagnosis included prurigo nodularis, vasculitis, nummular eczema and acquired perforating dermatosis. Laboratory investigation revealed high serum levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase and immunoglobulin G4. Anti-smooth muscle antibody (SMA) and anti-neutrophil cytoplasmic antibodies ANCA) were strongly positive; both PR3-ANCA and MPO-ANCA were detected. The patient had not had exposure to hepatotoxic drugs and an investigation ruled out HIV, hepatitis A, B and C infections. Liver biopsy demonstrated interface hepatitis with METAVIR fibrosis score F4, leading to the diagnosis of autoimmune sclerosing cholangitis (ASC). Skin biopsy was performed from a chronic nodular lesion on the left leg demonstrating transepidermal elimination of abnormal keratin with lymphohistiocytic infiltrate surrounding the epidermal downgrowth (Fig. 4). The histological features of keratotic plug filling an epidermal invagination and the lack of elastic and collagen fibers helped to establish the diagnosis of Kyrle’s disease (2, 3). The patient’s ASC was treated initially with systemic corticosteroids followed by maintenance therapy with azathioprine, ursodeoxycholic-acid and vitamins A, D, E, K. She was also given topical corticosteroids and tacrolimus. The rash improved significantly after 5 weeks of azathioprine therapy, parallel to the improvement of liver enzymes and the decreasing levels of IgG4, ANCAs and SMA. Resolution of the rash was noted after 4 months along with a complete control of the hepatic disease. This close correlation strengthens the causative relationship between ASC and Kyrle’s disease.

Fig. 3, 4: Kyrle’s disease in a 4-year-old girl.

Discussion. Kyrle’s disease (KD) is also known as hyperkeratosis follicularis et parafollicularis in cutem penetrans (3) and is classified as a subtype of acquired perforating dermatosis (APD). There are traditionally four classic perforating skin diseases: Kyrle’s disease (KD), elastosis perforans serpiginosa, reactive perforating collagenosis and perforating folliculitis. These perforating skin diseases can be differentiated from each other by clinical features as well as histological findings (1, 4, 5).
KD is extremely infrequent in children and is often associated with underlying chronic conditions, most typically renal disease and diabetes mellitus (2, 3), but congestive heart failure, hyperlipidemia, infective diseases such as HIV, and hepatic insufficiency were also described (1, 3, 5). To date, only one case report described an association between APD and sclerosing cholangitis in an adult patient (5).
Several treatment modalities have been reported in the literature for KD, such as emollients, keratolytics, corticosteroids, retinoids, antihistamines, antibiotics, immunosuppressants, phototherapy and various combination therapies. In addition, a significant improvement can be anticipated upon resolving the underlying condition (2), as occurred in our patient.
Conclusion. To our knowledge, the presented report is the first described case of ASC as an underlying condition for KD in a child. This case emphasizes the importance of this rare condition and the contribution the dermatologist could have in identifying a potentially life-threatening systemic disease.

Conflicts of interest
The Authors declare that they have no conflicts of interest.

Address to:
Dr. Andrea Izabella Gál
Department of Pediatric Dermatology
Heim Pál National Children’s Institute
1089 Budapest Üllői út 86 Hungary

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