Reactive Perforating Collagenosis

Article Author:
Tessa Mullins
Article Editor:
Patrick Zito
Updated:
8/3/2019 8:11:57 PM
PubMed Link:
Reactive Perforating Collagenosis

Introduction

Reactive perforating collagenosis is a rare skin disease that is has a characteristic transepidermal elimination of altered collagen through the epidermis. It occurs in two forms: an inherited form in childhood that is very rare and an acquired form in adulthood more commonly found in patients with diabetes mellitus and end-stage renal disease. It is one of four perforating transepithelial elimination disorders. Perforating dermatosis is a skin disease that is characterized by the transepidermal elimination of material in the dermis that can be divided into two groups: primary and secondary. Primary perforating dermatoses include reactive perforating collagenosis, Kyrle disease, elastosis perforans serpiginous and perforating folliculitis. Secondary perforating dermatoses was coined by Rapini in 1989 and is called acquired reactive perforating collagenosis. [1][2]Commonly, patients will have hyperkeratotic papules on the extensor areas of extremities and hands, most likely over areas of superficial trauma. The lesions are very pruritic and can grow into large, umbilicated papulonodules with a central keratotic plug that relapse and remit over the span of the patient’s lifetime. Most cases are self-limited and do not require treatment. Patients can be treated with avoidance of superficial trauma and control of pruritus in most cases.[3][4]

Etiology

The precise etiology and pathogenesis of reactive perforating collagenosis are unknown. The inherited form has had reported cases of autosomal dominant, autosomal recessive, and sporadic inheritance. It has been proposed that superficial trauma, genetic predisposition, micro vasculopathy, and calcium deposits in the skin may contribute to reactive perforating collagenosis.

Epidemiology

Reactive perforating collagenosis is a very rare inherited disease. Fewer than 50 cases have been reported in the literature since it was first described in 1967. The acquired form found in adults is more common and can occur in approximately ten percent of renal patients on hemodialysis. Reactive perforating collagenosis shows no racial predilection, although it has been noted that three of the five cases of the giant variant of acquired reactive perforating collagenosis have been found in Asians. Inherited and acquired reactive perforating collagenosis has been found equally in males and females. Most commonly, the inherited form presents in infancy or childhood, while the acquired form occurs in adults from their third to their fifth decade of life.[5][6]

Pathophysiology

There has been no specific genetic defect found. It has been reported that overexpression of TGF-beta3 and extracellular matrix proteins may be seen in patients with the acquired form of reactive perforating collagenosis. Although there has been no specific cause found, it appears as if the transepidermal elimination of collagen could be a simple reaction from pruritus or a defect in collagen leading to focal damage. Serum and tissue concentrations of fibronectin have been reported to be elevated which may contribute to epithelial migration. Superficial trauma, as well as a cold environment, induces degeneration of collagen. It has also been reported that the receptor for advanced glycation end products (RAGE) may play a role in the pathogenesis of acquired reactive perforating collagenosis. The receptor for advanced glycation end products plays a role in the inflammatory response pathway as a multiligand transmembrane receptor.

Histopathology

The histology of reactive perforating collagenosis classically shows transepidermal. Vertically oriented, cupping or invagination of the epidermis most commonly is seen. Vertically oriented perforating bundles of basophilic collagen are present at the bases of the invagination of the epidermis with focal extrusions. A keratin plug most likely is found in the cupping of the epidermis. Histology is variable depending on the stage of the lesion. New lesions will show epidermal hyperplasia, degenerated basophilic collagen fibers with later lesions showing invagination of the epidermis with a keratin plug. The vertically oriented basophilic collagen fibers are highlighted with Verhoeff-Van Gieson staining, which stains the collagen fibers red. This differentiates reactive perforating collagenosis to elastosis perforans serpiginosa which will not show any staining of elastic fibers.

History and Physical

The small, hyperkeratotic papules of reactive perforating collagenosis can be present in any area of the body. The inherited form begins in infancy as papules located on the extensor surfaces of the hands, elbows, and knees, most likely after superficial trauma to the area. Reactive perforating collagenosis lesions then grow into larger, umbilicated papulonodules with central adherent keratin plugging. The lesions will most commonly resolve spontaneously in six to eight weeks, leaving behind a hypopigmented area or scar. The patient will most likely complain of pruritus of the lesions. Koebner phenomenon of the lesions can occur. These lesions can occur, and most patients will experience a relapsing and remitting course of the disease throughout their life. Five cases reported of a giant variant of acquired reactive perforating collagenosis have been reported. In one case, a 60-year-old woman on hemodialysis presented with 1 cm to 10 cm papules with a central keratotic plug that showed transepidermal elimination of collagen on histology. She had a six-month history of pruritus with the lesions.[7][8][9][10]

Evaluation

A diagnosis of reactive perforating collagenosis is mostly clinical with recognition of classic histological findings. A punch biopsy is warranted for diagnosis. No lab or imaging studies are needed, and it is unlikely that they would be beneficial to the treatment or diagnosis of reactive perforating collagenosis. The differential diagnosis for reactive perforating collagenosis is similar to other perforating skin disorders. The differential can include folliculitis, arthropod bites, prurigo nodularis, multiple keratoacanthoma, and dermatofibroma. The physical and histologic findings, childhood onset, and family history help distinguish reactive perforating collagenosis from the previous diseases.

Treatment / Management

Reactive perforating collagenosis lesions are commonly self-limited and rarely problematic. The mainstay of treatment is avoiding trauma as to decrease risk factors for acquiring reactive perforating collagenosis lesions. Treatment is also aimed at controlling pruritus with topical corticosteroids, emollients, and systemic antihistamines. The use of keratolytics, topical and oral retinoids, phototherapy, liquid nitrogen, methotrexate, and allopurinol have been reported without much improvement of the lesions. No randomized controlled trials have evaluated the treatments for reactive perforating collagenosis, and all treatment suggestions are the result of case reports. It appears that treatment is patient specific and can vary with the degree of severity of the lesions. Most lesions will regress spontaneously in six to eight weeks with hypopigmentation, scarring, or post-inflammatory hyperpigmentation. Unfortunately, most patients will have a relapsing and remitting course of lesions throughout their life.[11][10]

Enhancing Healthcare Team Outcomes

Reactive perforating collagenosis is a rare benign skin disorder. When the primary care provider, nurse practitioner and internist see patients with skin disorders, they should be referred to a dermatologist to confirm the diagnosis. The mainstay of treatment is avoiding trauma as to decrease risk factors for acquiring reactive perforating collagenosis lesions. Treatment is also aimed at controlling pruritus with topical corticosteroids, emollients, and systemic antihistamines. The use of keratolytics, topical and oral retinoids, phototherapy, liquid nitrogen, methotrexate, and allopurinol have been reported without much improvement of the lesions. No randomized controlled trials have evaluated the treatments for reactive perforating collagenosis, and all treatment suggestions are the result of case reports. Unfortunately, most patients will have a relapsing and remitting course of lesions throughout their life. Typically these patients are managed chronically by a dermatologist, nurse practitioner, and nurse specializing in dermatology. The patients require regular follow up visits, close monitoring, and education in regards to the disease process and treatment. Generally, the nurse practitioner and nurse can manage followup and involve the dermatologist if there are concerns such as a progression of the disease or the pruritis becomes intractable. The best care of these patients to produce the best outcome is an interprofessional team managing treatment, patient education, and follow up. [Level V]


References

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