Acquired Reactive Perforating Collagenosis

Acquired reactive perforating collagenosis (ARPC) is commonly recognized as an unusual skin reaction to superficial trauma that is observed in patients with a certain genetic predisposition or underlying diseases, such as diabetes mellitus or renal diseases. We present the unusual case of a 55-year-old female diabetic patient with numerous characteristic dome-shaped nodules, which consisted of central umbilication containing firm keratotic plugs.


Introduction
Acquired reactive perforating collagenosis (ARPC) is a skin disorder that is characterized by the transepidermal elimination of altered collagen through the epidermis [1].An inherited form was first described by Mehregan et al. [2] in 1967.The adult form, which commonly manifests in diabetics, has been reported in 10% of patients undergoing dialysis and has been mostly ascribed to diabetic nephropathy [3].We hereby describe a case of acquired reactive perforating collagenosis in a patient with diabetes mellitus.

Case Report
A 55-year-old woman presented with a 4 month history of skin eruption and pruritus on her lower extremities.She had an 18 year history of type 2 diabetes mellitus that was treated with subcutaneous insulin injections.The skin eruptions developed on both legs.At the time of presentation, there were numerous dome-shaped nodules, which were characterized by central umbilications containing firm keratotic plugs, and erythema was observed around the nodules (Figure 1).Comprehensive laboratory investigations revealed no signs of renal dysfunction, including a urea level of 52 mg/ dL and a creatinine level of 0.8 mg/dL; however, the mean fasting blood glucose level was 155 mg/dL, and there was an elevated glycosylated hemoglobin of 8.6%.The patient did not have a renal disorder due to the diabetes mellitus.Histopathological evaluation of a representative skin lesion showed transepidermal elimination of necrotic collagen bundles into a cup-shaped epidermal depression.Numerous neutrophil polymorphonuclears were observed.Marked neutrophilia, in addition to mononuclear cell infiltration particularly of macrophages and giant cells, was observed under the dome-shaped lesions and debris (Figure 2).Van Gieson simple staining showed degenerated collagen fibers that had perforated through the epidermis (Figure 3).Therefore, an ARPC diagnosis was verified, and the patient was referred to an endocrinologist for the management of her diabetes mellitus and underwent narrow UVB treatment, without significant amelioration.

Discussion
Perforating disorders are uncommon diseases that are histopathologically characterized by transepidermal elimination and include reactive perforating collagenosis, elastosis perforans serpiginosa, Kyrle's disease and perforating folliculitis [4].This classification was made according to the type of epidermal damage and the characteristics of the eliminated material [5].The pathogenesis of ARPC is unknown.As originally postulated by Mehregan et al. [2], "mild superficial trauma in genetically susceptible persons leads to necrobiosis of collagen in dermal papillae, which is subsequently eliminated from the dermis by means of transepithelial elimination, " still seems to be correct.In ARPC, the defect occurs in the papillary dermis where histochemically altered but ultrastructurally intact-type IV collagen is present; the collagen is surrounded and engulfed by focal epidermal proliferation.A central crater containing inflammatory cells, keratinous material and altered collagen then develops and the altered collagen is subsequently expelled by transepithelial migration [6].ARPC has been observed in association with multiple disorders, including diabetes mellitus, renal failure, hyperparathyroidism, liver disease, neurodermatitis, IgA nephropathy, periampullary carcinoma with jaundice, adenocarcinoma and liver neoplasms [7].
The disease presents clinically as umbilicated papules with a central adherent keratotic plug [8].The hands and legs are frequently involved.In most cases of ARPC, patients experience severe pruritus and Köbner's phenomenon.Thus, it is thought that traumatic stimulation, such as scratching, induces the transepidermal elimination of the degenerated collagen fibers [9[.Severe pruritus and Köbner's phenomenon were present in our patient.
The possible biochemical or immunological mechanisms of the systemic diseases that are potentially responsible for the development and appearance of ARPC are still under investigation [10].There is no specific treatment for ARPC.Topical and oral retinoids and topical and intralesional glucocorticoids have been reported to be effective in some patients in a case series [11].In addition, individual lesions can be excised.Tretinoin 0.1% cream may also be effective.ARPC is usually refractory to treatment; however, there have been reports of ARPC that has been successfully treated with phototherapy.The course of this disease is chronic, and if the associated diseases are treated, patients may have a better prognosis [12].
In conclusion ARPC is a rare disease in terms of the clinical and histological findings.In the presence of diabetes mellitus and severe pruritus, ARPC must be considered in the differential diagnosis.

Figure 2 .
Figure 2. Transepidermal elimination of necrotic collagen bundles into a cup-shaped epidermal depression.