When a 66-Year-Old Patient Presents With Umbilicated, Pruritic Papules

This piece originally appeared in The Dermatologist and is adapted with permission. To access the original article, visit https://tinyurl.com/4psp9vce.

A 66-year-old man with no past medical history presented with a pruritic eruption on the bilateral lower extremities of approximately 3 weeks’ duration. His surgical, family, and social history, along with allergies, were all unremarkable. The patient endorsed possible chigger bites while working on his farm prior to the appearance of the rash. He related no other potential inciting event. The lesions started as papules that subsequently became umbilicated. On physical exam, there were numerous umbilicated, crusted papules and plaques with erythematous borders involving the bilateral anterior lower extremities up to the distal thigh (Figure 1). There was no odor, drainage, cellulitis, or signs of infection noted. The patient had not undergone any prior treatment for this concern.

Upon evaluation, the team ordered a complete blood count, comprehensive metabolic panel, antinuclear antibodies, and protein electrophoresis, which were all within normal limits. A punch biopsy revealed a central crater containing parakeratotic debris, basophilic debris, extrusion of collagen fibers, and a mixed inflammatory infiltrate (Figure 2).

Key Questions To Consider

1.    What might one include in the differential diagnosis?
2.    What important triggering factor is a part of the history of present illness?
3.    What diagnostic steps are prudent in this case?
4.    What treatment options exist for this condition?

Answering The Key Diagnostic Questions

1.    Prurigo nodularis and other traditionally recognized perforating disorders of elastosis perforans serpiginosa (EPS), perforating folliculitis, and Kyrle’s disease are among the differential diagnoses.
2.    Trauma induced by scratching must undergo consideration as a potential trigger.
3.    Focused history and physical examination, punch biopsy, and careful consideration of the evidence, as the diagnosis is usually clinical.
4.    Treatment focuses primarily on addressing pruritus and managing comorbid conditions. Reports also cite narrowband (NB) UV-B, allopurinol, topical doxycycline and systemic retinoids, topical and intralesional steroids, usually in combination with antihistamines, and topical combination of benzoyl peroxide and steroids, among others as options.^{18,32, 35-41}

What Is Acquired Reactive Perforating Collagenosis?

The clinical and histopathologic findings were that of reactive perforating collagenosis (RPC). RPC was first described in 1967 as an unusual reaction to superficial trauma.¹ Because the original description was of a child, it represented the now known familial variant. Mehregan and colleagues¹ described the life of the lesions in both clinical and histopathologic detail. The eruption initially presented as pruritic, skin-colored papules that became umbilicated with a central keratinaceous plug, which then enlarged to 4 mm to 6 mm over 3 to 5 weeks with the keratinaceous plug acquiring a brown, leathery, and deeply adherent quality. The lesions then finally entered a phase of regression and completely resolved within 6 to 8 weeks. Histopathologically, a fully developed, umbilicated lesion showed extrusion of vertically oriented collagen fibers amid a basophilic papillary dermis and parakeratotic debris.¹ One can confirm that the extruded material is collagen via Masson’s trichome stain.²

Subsequently, descriptions arose of identical lesions in older adults, usually in association with diabetes and renal disease.^3-6 Rarely, cases of acquired RPC appear without systemic disease such as the case presented herein.⁷ In contrast to the familial variant, the clinical course is often protracted.^7,8

Although Mehregan and team1 noted an absence of elastic fibers within the devitalized plug in the original description, some studies demonstrated extrusion of elastin fibers as well.^9-11 As a result, some authors advocate the term “acquired perforating dermatosis,” because there seems to be considerable overlap and disagreement on the classification and features of the classically described perforating disorders (Table 1).¹⁰

Although the etiopathogenesis of RPC is poorly understood, it is accepted that trauma induced by scratching seems to be an important triggering factor. This observation explains the frequent Koebnerization of lesions and the numerous cases linked to scabies infestation, or more rarely, to exacerbations of atopic dermatitis.^11,17-20 Some authors proposed that vasculopathy, subsequent hypoxia, and dermal necrosis in response to trauma are the key factors in this disease.⁶ Other theories include deposition of byproducts of chronic kidney disease within the dermis while others highlight the potential role of polymorphonuclear cells with the release of lysosomal enzymes in its pathogenesis.^5,21,22 Ultrastructurally, the eliminated collagen is not degenerated and showed normal periodicity.^23,24 The role of glycated collagen I and III in the mechanism of transepithelial elimination was explored in cell cultures, where exposing keratinocytes to these advanced glycation end products induced terminal differentiation of keratinocytes through the AGE-receptor CD36 with concomitant and upward movement of keratinocytes and collagen.²⁵ Finally, there is documentation of overexpression of transforming growth factor beta-3 (TGFB-3), an important peptide in tissue repair, by immunohistochemistry.^26,27

Understanding the Differential Diagnosis

The differential diagnosis of RPC includes prurigo nodularis and the other traditionally recognized perforating disorders of elastosis perforans serpiginosa (EPS), perforating folliculitis, and Kyrle’s disease. Characteristics of EPS include its classical serpiginous or annular distribution of keratotic papules with preferential involvement of the back or sides of neck and frequent association to genetic disorders such as Down syndrome, Marfan syndrome, Ehler Danlos, osteogenesis imperfecta, pseudoexanthoma elasticum, and long-term use of penicillamine.¹² By histology, there is elimination of elastic fibers through perforating epithelial channels along with an increase in elastic fibers in the dermis.¹² Perforating folliculitis consists of an asymptomatic to pruriginous, discrete follicular papules with a central keratinous plug.¹³ Although it can be seen in association with chronic kidney disease, it is often seen in the absence of systemic disease and more recently also associated with the use of kinase inhibitors such as sorafenib.^28-30 On histopathology, there is a dilated hair follicle plugged with keratinous material and necrotic crust. Serial sectioning reveals the areas of perforation located at the level of the follicular infundibulum where elastic fibers, necrotic connective tissue, and degenerated inflammatory cells access the follicular cavity. In the near vicinity of this area, a curled hair shaft may be seen.³¹

Kyrle’s disease is considered a controversial entity by several authors; many cases described in the literature as such were reclassified to represent RPC or the end-stage of other disorders including perforating folliculitis.^10,31 Strict criteria to diagnose this disorder as described by Kyrle¹⁴ and reviewed by Carter and Constantine^15,16 include a chronic popular eruption with a cone-shaped hyperkeratotic plug that may or may not involve the hair follicles. Histopathology shows a keratotic plug with basophilic debris and parakeratosis which may also involve the basal layer where epidermal disruption occurs. In this focus, one usually sees a dermal granulomatous reaction. Importantly, there is no extrusion of elastic fibers. This entity can also be associated with renal failure and diabetes mellitus.^32,33

Prurigo nodularis is a chronic dermatosis characterized by dome-shaped papulonodules distributed symmetrically in areas accessible to scratching such as the extensor surfaces of extremities and trunk. The lesions may have a central scale, crust, or ulcerations. The diagnosis is usually clinical. Of note, some authors describe the umbilicated variant of prurigo nodularis and propose that acquired reactive perforating dermatosis is a variant of it.³⁴ This view, however, is not universally accepted and the cases described were in the setting of diabetes mellitus and chronic kidney disease. Additionally, when evaluated by histopathology, some showed extrusion of collagen fibers within the plug.¹³

Management of Reactive Perforating Collagenosis

Treatment of acquired RPC is challenging, with no clinical trials available to recommend a standard treatment. Evaluation of treatment efficacies is also confounded by the fact that some lesions may spontaneously self-involute. Efforts should focus on controlling the pruritus and referral to appropriate team members to manage comorbid diseases. Case series and case reports showed efficacy of narrowband (NB) UV-B, allopurinol, topical doxycycline and systemic retinoids, topical and intralesional steroids, usually in combination with antihistamines, and topical combination of benzoyl peroxide and steroids among others.^18,32,35-41

Concluding Thoughts

This case highlights the clinical presentation of acquired RPC likely triggered by chigger bites in a patient without systemic disease. In this particular case, the patient underwent three sessions of NB-UVB with improvement and was lost to follow-up. As others have hypothesized, it is a further piece of evidence that the trauma induced by scratching may play an important role in the formation of lesions.

Dr. Grayson is a PGY-1 at Florida State University College of Medicine internal medicine residency program in Tallahassee, FL.

Dr. Deschaine is a PGY-4 at Florida State University College of Medicine dermatology residency program.

Dr. Cohen is a clinical physician at University of Florida Department of Dermatology in Gainesville, FL.

Dr. Johnson is a clinical assistant professor at University of Florida Department of Dermatology.

Editor’s Note: For more engaging patient case presentations, see our other Dermatology Diagnosis columns that appear in print and online. The Podiatric Dermatology Resource Center also showcases the latest diagnostic concepts and therapeutic pathways, along with podcasts and more.

References
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