History
Small, keratotic papules develop after minor trauma. The lesions start as pin-sized lesions, and they grow into larger papules/nodules over a few weeks. They heal with minor scarring. In acquired perforating collagenosis, patients typically present with umbilicated papules and plaques on the extremities and trunk. [7]
Intense pruritus is a feature of the acquired form of reactive perforating collagenosis. Many patients have diabetes mellitus or renal failure, and many will be on hemodialysis.
A positive family history may be elicited in the childhood form of reactive perforating collagenosis.
Physical Examination
Skin lesions of reactive perforating collagenosis
Flesh-colored, umbilicated, dome-shaped papules or nodules as large as 10 mm in diameter are typical. They have an adherent, keratinous plug. A giant variant of reactive perforating collagenosis has been described. [8]
Reactive perforating collagenosis lesions may occur in a linear configuration, exhibiting the Koebner phenomenon.
Residual scarring may be seen from previously healed lesions.
Skin distribution of reactive perforating collagenosis
Lesions are most commonly found on the extensor surfaces of the limbs and the dorsa of the hands. Reactive perforating collagenosis lesions may also occur on the trunk and the face.
(See the image below.)
Causes
The childhood form of reactive perforating collagenosis is inherited. [9] A number of affected families have been reported. The mode of inheritance is not clear. Reports of affected families reveal autosomal dominant inheritance, autosomal recessive inheritance, and sporadic cases.
A case has been described arising in a child with Down syndrome. [10]
The underlying cause of reactive perforating collagenosis is unknown, but an abnormal response to superficial trauma (eg, scratching) may be involved. Papules have been reported following scratches, acne spots, insect bites, [1] and scabies. [11] Lesions of reactive perforating collagenosis have been experimentally induced in susceptible skin by scratching. [12]
The acquired form of reactive perforating collagenosis may occur in association with chronic renal failure, often in a patient with underlying diabetes mellitus. In both the United Kingdom and the United States, the prevalence of this disorder in patients on dialysis is approximately 10%. [5, 6] While the pathogenesis of acquired perforating collagenosis is not well-understood, there appears to be a genetic component in some cases. Also, it has been suggested that microvasculopathy and trauma may act as triggers for collagen transdermal elimination and degeneration. [7]
The acquired form of reactive perforating collagenosis also can occur in association with other nephropathies without diabetes. Interestingly, both Akoglu et al and Bellinato et al found evidence that increased advanced glycation end-products may play a role in acquired perforating collagenosis pathogenesis. [13, 14] Akoglu et al reported discovering overexpression of the receptor for advanced glycation end-products in an analysis of 41 patients, independent of diabetes status. [13]
Acquired reactive perforating collagenosis has been reported in association with hypothyroidism, hyperparathyroidism, liver dysfunction, [4] dermatomyositis, [15] and rheumatoid vasculitis. [16] In a single case, a woman was initially diagnosed with polymorphic eruption of pregnancy at 17 weeks' gestation. Her skin condition evolved morphologically, and she was reevaluated at 24 weeks' gestation and diagnosed with acquired reactive perforating collagenosis. [17]
Malignancies, including lymphoma, hepatocellular carcinoma, [18] periampullary carcinoma, [19] and thyroid cancer, [20] have been associated with the acquired form of reactive perforating collagenosis.
Indinavir has induced reactive perforating dermatosis in 2 patients with HIV disease, and sorafenib was associated with acquired reactive perforating collagenosis in a single patient with HIV. [21, 22] . Ranibizumab injections have also been associated with acquired reactive perforating collagenosis, but the condition resolved after the patient was switched to aflibercept. [23]
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Typical keratotic papules.
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Cup-shaped invagination of the epidermis associated with a keratin plug containing inflammatory debris and collagen fibers.
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Vertically orientated collagen fibers are extruded into the overlying keratin plug.
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An elastic van Gieson stain demonstrating the expulsion of collagen fibers (red) into the overlying keratin plug.
