eMedicine Specialties > Dermatology > Diseases of the Dermis

Reactive Perforating Collagenosis

Susan Cooper, MB, ChB, MD, MRCGP, MRCP, Consultant Dermatologist and Honorary Senior Clinical Lecturer, Department of Dermatology, Churchill Hospital, Oxford, United Kingdom
Ruth G Asher, MBChB, FRCPath, Locum Consultant Dermatopathologist, John Radcliffe Hospital, Oxford

Updated: Oct 30, 2009

Introduction

Background

Reactive perforating collagenosis is a rare skin disorder characterized by the transepidermal elimination of altered collagen through the epidermis. The 2 distinct forms of are an inherited form that manifests in childhood and an acquired sporadic form that occurs in adulthood.

The 4 primary perforating diseases are reactive perforating collagenosis, elastosis perforans serpiginosum, Kyrle disease, and perforating folliculitis, although whether perforating folliculitis is a primary perforating disease has been questioned, given that ruptured follicles are a feature of many infective conditions.

Some authors reserve the term reactive perforating collagenosis for the rare inherited form of the disease, preferring the term acquired perforating dermatosis for the acquired form. This article describes both inherited reactive perforating collagenosis and acquired reactive perforating collagenosis.

Pathophysiology

The major abnormality in reactive perforating collagenosis is focal damage to collagen and the elimination of the disrupted collagen through the epidermis.¹ A frequent association with pruritus, the tendency to the Koebner phenomenon and the distribution of lesions on trauma-prone areas provides evidence that superficial trauma (eg, scratching) may play a part in the etiology of reactive perforating collagenosis. Cold may precipitate the lesions, especially in the inherited form.

The acquired form usually occurs in patients with diabetes or chronic renal failure, especially those receiving dialysis. Other associations with systemic diseases, such as malignancy, have been reported.

Faver et al has proposed diagnostic criteria for the adult (acquired) form of reactive perforating collagenosis, as follows² :

• Elimination of necrotic basophilic collagen bundles into a cup-shaped epidermal depression as seen in biopsy specimens
• Umbilicated papules or nodules with a central, adherent keratotic plug
• Onset of lesions after age 18 years

Frequency

International

• Inherited reactive perforating collagenosis is a rare disorder. Fewer than 50 cases of inherited reactive perforating collagenosis have been reported.
• The acquired form of reactive perforating collagenosis is more common, occurring in as many as 10% of patients receiving maintenance hemodialysis.^3,4

Mortality/Morbidity

• The lesions of reactive perforating collagenosis are intensely itchy, leaving some scarring after resolution. The lesions of reactive perforating collagenosis often occur on a background of very itchy skin.

Race

• No racial variations in the incidence of reactive perforating collagenosis are reported.

Sex

• The sexual incidence of reactive perforating collagenosis is equal.

Age

• The inherited form of reactive perforating collagenosis usually presents in infancy or early childhood.
• The acquired form of reactive perforating collagenosis occurs in adults. In a series of 22 patients with acquired reactive perforating collagenosis, the mean patient age at presentation was 56 years.²

Clinical

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.
• Intense pruritus is a feature of the acquired form of reactive perforating collagenosis. Many patients have diabetes 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

• 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.⁵
  • 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.

Typical keratotic papules.

Causes

• The childhood form of reactive perforating collagenosis is inherited.⁶ 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.
• 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,⁷ and scabies.⁸ Lesions of reactive perforating collagenosis have been experimentally induced in susceptible skin by scratching.⁹
• The acquired form of reactive perforating collagenosis may occur in association with chronic renal failure, often in a patient with underlying diabetes. In both the United Kingdom and the United States, the prevalence of this disorder in patients on dialysis is approximately 10%.^3,4
• The acquired form of reactive perforating collagenosis also can occur in association with other nephropathies without diabetes.
• Acquired reactive perforating collagenosis has been reported in association with hypothyroidism, hyperparathyroidism, and liver dysfunction.²
• Malignancies, including lymphoma, hepatocellular carcinoma,¹⁰ periampullary carcinoma,¹¹ and thyroid cancer,¹² have been associated with the acquired form of reactive perforating collagenosis.
• Indinavir has induced reactive perforating dermatosis in 2 patients with HIV disease.¹³

Differential Diagnoses

Elastosis Perforans Serpiginosum
Kyrle Disease
Perforating Folliculitis
Prurigo Nodularis

Workup

Laboratory Studies

• The purpose of any investigation is to search for underlying causes, particularly causes of pruritus.
• Urea and creatinine determinations are needed to detect any underlying renal impairment. A creatinine clearance test and other more complex renal investigations may be required.
• Ferritin levels and a full blood cell count can help detect anemia. Low iron stores can cause pruritus.
• Random glucose testing can help detect diabetes.
• Skin biopsy is essential to make a diagnosis.

Histologic Findings

The histology varies with the stage of the reactive perforating collagenosis. Early lesions show epidermal hyperplasia associated with underlying degenerate basophilic collagen fibers. In established lesions, a cup-shaped depression of the epidermis associated with a keratin plug containing parakeratosis, inflammatory debris and collagen fibers can be seen.
 

Cup-shaped invagination of the epidermis associated with a keratin plug containing inflammatory debris and collagen fibers.

Vertically orientated collagen fibers are extruded into the overlying keratin plug.

An elastic van Gieson stain demonstrating the expulsion of collagen fibers (red) into the overlying keratin plug.

Treatment

Medical Care

Treatment of reactive perforating collagenosis lesions is often unsatisfactory; in many cases, the lesions are self-healing, but usually are recurrent.

• Anecdotal reports describe successful therapy for reactive perforating collagenosis with retinoids,¹⁴ allopurinol,⁵ doxycycline,¹⁵ UVB,¹⁶ and psoralen ultraviolet light A.¹⁷ Phototherapy is a good choice for patients with coexistent renal disease and associated pruritus.
• Topical steroids are usually not helpful, but intralesional steroids have been successful.⁷
• Emollients and systemic antihistamines seem helpful in controlling pruritus.

Follow-up

Complications

• The inherited form of reactive perforating collagenosis is not associated with any systemic complications.
• The acquired form of reactive perforating collagenosis occurs in patients with multiple medical problems, but whether the development of the lesions implies a poorer prognosis is unclear.

Miscellaneous

Medicolegal Pitfalls

• The major problem is misdiagnosis of reactive perforating collagenosis and confusion with other perforating disorders.

Multimedia

Media file 1: Typical keratotic papules.

Media file 2: Cup-shaped invagination of the epidermis associated with a keratin plug containing inflammatory debris and collagen fibers.

Media file 3: Vertically orientated collagen fibers are extruded into the overlying keratin plug.

Media file 4: An elastic van Gieson stain demonstrating the expulsion of collagen fibers (red) into the overlying keratin plug.

References

1. Millard PR, Young E, Harrison DE, Wojnarowska F. Reactive perforating collagenosis: light, ultrastructural and immunohistological studies. Histopathology. Oct 1986;10(10):1047-56. [Medline].

2. Faver IR, Daoud MS, Su WP. Acquired reactive perforating collagenosis. Report of six cases and review of the literature. J Am Acad Dermatol. Apr 1994;30(4):575-80. [Medline].

3. Morton CA, Henderson IS, Jones MC, Lowe JG. Acquired perforating dermatosis in a British dialysis population. Br J Dermatol. Nov 1996;135(5):671-7. [Medline].

4. Poliak SC, Lebwohl MG, Parris A, Prioleau PG. Reactive perforating collagenosis associated with diabetes mellitus. N Engl J Med. Jan 14 1982;306(2):81-4. [Medline].

5. Hoque SR, Ameen M, Holden CA. Acquired reactive perforating collagenosis: four patients with a giant variant treated with allopurinol. Br J Dermatol. Apr 2006;154(4):759-62. [Medline].

6. Ramesh V, Sood N, Kubba A, Singh B, Makkar R. Familial reactive perforating collagenosis: a clinical, histopathological study of 10 cases. J Eur Acad Dermatol Venereol. Jul 2007;21(6):766-70. [Medline].

7. Kim EJ, Kim MY, Kim HO, Park YM. Acquired reactive perforating collagenosis triggered by insect bite. J Dermatol. Sep 2007;34(9):677-9. [Medline].

8. Ikezaki E, Sugita K, Kabashima K, Tokura Y. Scabies-induced acquired reactive perforating collagenosis. J Eur Acad Dermatol Venereol. Jan 2008;22(1):120-1. [Medline].

9. Bovenmyer DA. Reactive perforating collagenosis. Experimental production of the lesion. Arch Dermatol. Sep 1970;102(3):313-7. [Medline].

10. Kiliç A, Gönül M, Cakmak SK, Gül U, Demiriz M. Acquired reactive perforating collagenosis as a presenting sign of hepatocellular carcinoma. Eur J Dermatol. Jul-Aug 2006;16(4):447. [Medline].

11. Chae KS, Park YM, Cho SH, Cho BK. Reactive perforating collagenosis associated with periampullary carcinoma. Br J Dermatol. Sep 1998;139(3):548-50. [Medline].

12. Yazdi S, Saadat P, Young S, Hamidi R, Vadmal MS. Acquired reactive perforating collagenosis associated with papillary thyroid carcinoma: a paraneoplastic phenomenon?. Clin Exp Dermatol. May 5 2009;[Medline].

13. Calista D, Morri M. Acquired reactive perforating collagenosis induced by indinavir in 2 patients with HIV disease. Eur J Dermatol. Jan-Feb 2008;18(1):84-5. [Medline].

14. Berger RS. Reactive perforating collagenosis of renal failure/diabetes responsive to topical retinoic acid. Cutis. Jun 1989;43(6):540-2. [Medline].

15. Brinkmeier T, Schaller J, Herbst RA, Frosch PJ. Successful treatment of acquired reactive perforating collagenosis with doxycycline. Acta Derm Venereol. 2002;82(5):393-5. [Medline].

16. Vion B, Frenk E. [Acquired reactive collagen disease in the adult: successful treatment with UV-B light]. Hautarzt. Jul 1989;40(7):448-50. [Medline].

17. Serrano G, Aliaga A, Lorente M. Reactive perforating collagenosis responsive to PUVA. Int J Dermatol. Mar 1988;27(2):118-9. [Medline].

Keywords

reactive perforating collagenosis, acquired perforating dermatosis, perforating disorders, Kyrle's disease, elastosis perforans serpiginosa, perforating folliculitis

Contributor Information and Disclosures

Author

Susan Cooper, MB, ChB, MD, MRCGP, MRCP, Consultant Dermatologist and Honorary Senior Clinical Lecturer, Department of Dermatology, Churchill Hospital, Oxford, United Kingdom
Susan Cooper, MB, ChB, MD, MRCGP, MRCP is a member of the following medical societies: Royal College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Ruth G Asher, MBChB, FRCPath, Locum Consultant Dermatopathologist, John Radcliffe Hospital, Oxford
Ruth G Asher, MBChB, FRCPath is a member of the following medical societies: Association of Clinical Pathologists, British Society of Dermatopathology, International Academy of Pathology, International Society of Dermatopathology, and Royal Society of Medicine
Disclosure: Nothing to disclose.

Medical Editor

James W Patterson, MD, Director of Dermatopathology, Professor of Pathology and Dermatology, Departments of Pathology and Dermatology, University of Virginia Medical Center
James W Patterson, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Medical Association, American Society of Dermatopathology, Medical Society of Virginia, Royal Society of Medicine, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Rosalie Elenitsas, MD, Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology
Disclosure: Nothing to disclose.

CME Editor

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Kristiana Gray, MD, to the development and writing of this article.

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