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Acquired reactive perforating collagenosis
Acquired reactive perforating collagenosis Report of six cases and review of the literature Inacio R. Faver, MD, Mazen S. Daoud, MD, and W. P. Daniel Su, MD
Rochester, Minnesota Background: Reactive perforating collagenosis (RPC) is characterized by transepithelial
elimination of altered collagen. Two types havebeen recognized: the childhood form and the adult form. Objective: Our purpose was to review the associated disorders, evaluate the possible causes, and set criteria for the diagnosis of the disease. Methods: The clinicaland pathologicfindings of six patients with the adult form of RPC are reviewed. The literature on this subject is compared with our findings. Results: Pruritus was reported in all cases.Treatment of pruritus cleared the lesions in many patients.This is the first report of an association between RPC and hyperparathyroidism, hypothyroidism, liver disorders, and neurodermatitis. Conclusion: Variousdisorders can be associatedwith the adult form of RPC. Pruritus is the common factor among all types. Control of itching might be helpful for clearing the lesions. We proposethe following diagnosticcriteria for acquired RPC: (1) histopathologic findings of elimination of necrotic basophilic collagen tissueinto a cup-shaped epidermal depression, (2) clinicalpresentation of umbilicated papules or nodules with a central adherent keratotic plug, and (3) onset of skin lesions after the age of 18 years. (J AM ACAD DERMATOL 1994;30:575-80.)
Reactive perforating collagenosis (RPC) is an uncommon condition described in 1967 by Mehregan et a1. 1 as a disease in which altered collagen bundles are eliminated through the epidermis. RPC occurs in two forms: childhood or inherited form, and adult or acquired form. Both forms are believed to be a cutaneous response to superficial trauma.v 3 We describe six patients with the adult (acquired) form ofRPC, reviewthe literature, and compare the clinical features, pathologic findings, associated disorders, and treatment of all published cases. METHODS We identified six patients with a diagnosis of the adult form of RPC at the Mayo Clinic between 1983 and 1992. Charts were reviewed for clinical data. All tissue specimens were obtained by punch biopsy, fixed in 10%
From the Department ofDermatology, Mayo Clinic and Mayo Foundation, Rochester, Minn. Dr. Faver isa visiting clinician at the Department ofDermatology. Accepted for publication Sept. 20, 1993. Reprint requests: W. P. Daniel Su, MD, Department ofDermatology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Copyright @ 1994 by the American Academy ofDermatology, Inc. 0190-9622/94 $3.00 + 0 16/1/51556
formalin, step-sectioned, and stained with hematoxylin and eosin, Schmidt's elastic-Giemsa, and Masson's trichrome stains.The literature on perforating collagenosis was reviewed. CASE REPORT A 43-year-old white man was seen in November 1988 for generalized pruritus that started after he began peritoneal dialysis in July 1984 for chronic kidney failure. He also noticed increased pigmentation and dryness of his skin.Treatment with antihistamines and topical moisturizers produced a limited response. Hemodialysis was started in June 1988, and the patient noticed increasing intensity of his itching associated with an eruption of small papules. Examination revealed multiple linear prurigo-like papules (Fig. 1) with a keratotic central plug (Fig. 2) on the arms, posterior aspect of the scalp, trunk, thighs, and buttocks. The biopsyspecimen wasconsistent with RPC. The patient was treated with topical steroids and wet dressings; 80% improvement was achieved and treatment with UVB was started. The patient was free of RPC within 6 weeks. RESULTS
Table I summarizes the clinical features of all cases that we regard as fulfilling the criteria for the adult (acquired) form of RPC in the literature, in-
575
576
Journal of the American Academy of Dermatology April 1994
Faver et al.
Case
Associated disorders
(author)
1 (Poliak et a1.4)
41/F/B
2
51/F/B
3
80/M/B
4
57/F/H
5
77/M/H
6
65/M/B
7 (Cochran et al. 5) 8
41/F/B 36JF/B
9 (Panzini and Dore6)
56/F/W
10 (Pedragosa et a1. 7)
49/F
11
43/M
12 (Vion and Frenk'')
77/M/W
13 (Berger")
53/M/B
14 (Bank et a1. IO)
38/M/B
15 (Henry et aLII)
35/F/A
16 (Cohen and Auerbach 12)
79/M/W
DM, retinopathy, nephropathy, PVD DM, retinopathy, nephropathy, PVD DM, retinopathy, nephropathy, PVD DM, retinopathy, nephropathy, PVD DM, retinopathy DM, retinopathy, nephropathy, PVD IDDM, retinopathy, nephropathy IDDM, nephropathy IDDM, retinopathy, COPD, HTN, nephropathy, cardiomyopathy, PVD Hodgkin's disease (nodular sclerosis type) Hodgkin's disease (nodular sclerosis type) NIDDM, nephropathy, vitiligo NIDDM, nephropathy, PVD AIDS, HIV, or heroin nephropathy Mixed histiocytic-lymphocytic lymphoma NIDDM, retinopathy
Distribution
Extensor surfaces of extremities Trunk, forehead, extensor surfaces of extremities Trunk, face , extensor surfaces of extremities Trunk, extensor surfaces of extremities Trunk, extensor surfaces of extremities Extensor surfaces of extremities Knees , arms, trunk Upper part of back, extensor surfaces of arms Upper limbs, lower part of back
Predominantly on legs Trunk, abdomen, upper limbs Legs, lower abdomen Chest, arms, legs, dorsum of both feet Extensor surfaces of forearms Arms, legs. back
Presen t cases
17
71/M/W
18
63/F/W
19
54/F/W
20
66/M/W
21
43/M/W
22
56/F/W
Nephropathy, cardiomyopathy, liver dysfunction, ascites, anemia, hyperparathyroidism, PVD, COPD Chronic pruritus ani, anal fissure, neurodermatitis, hypothyroidism, HTN Chronic active hepatitis, liver cirrhosis, NIDDM NIDDM, mild kidney failure, hypothyroidism, PVD Glomerulonephritis, CRF, mild NIDDM, obesity , pericardial tamponade, chronic anemia NIDDM, nephropathy, retinopathy, anemia, hypothyroidism, hyperlipidemia. CAD, HTN
Arms, legs
Buttocks, back , scalp
Dorsal forearms, hands. upper part of back One lesion on eyebrow Arms, posterior scalp, trunk, thighs, buttocks Arms, legs, trunk
+, Mild; ++. moderate; +++, severe; A , Asian; B, black; CAD, coronaryartery disease; C-MOPP, cyclophosphamide, nitrogen mustard, vincristine, prednisone.and procarbazine; COPD, chronic obstructive pulmonarydisease; CRF, chronicrenal failure; DM, diabetes mellitus; DTIC, dacarbazine; H, H ispanic; HTN, hypertension; lDDA-f, insulin-dependent diabetes mellitus; NA , not available; NlDDM, non-insulin-dependent diabetesmellitus; PVD, peripheral vascular disease; UVB, ultraviolet light B; W, white,
Journal of the American Academy of Dermatology Volume 30, Number 4
Relation to dialysis
Faver et al. 577
Pruritus
Koebner phenomenon
Treatment/Improvement
++
Yes
NA
No dialysis
+++
Yes
NA
I yr before dialysis
+++
Yes
NA
No dialysis
+++
Yes
NA
No dialysis
+++
Yes
NA
++
Yes
NA
Few mo after dialysis 2 yr after dialysis
+++ +++
Yes Yes
UVB/Resolved in 3 mo UVB/Undergoing treatment
No dialysis
+++
No
Retinoic acid/improved
No dialysis
NA
NA
No dialysis
+++
NA
Doxorubicin, bleomycin, DTIC, vinblastine/No improvement C-MOPP/deared in 6 rno
Simultaneously with dialysis
+++ +
Yes NA
5 mo after dialysis
+++
NA
No dialysis
++
Yes
No dialysis
+++
Yes
Diabetes control/Resolved in 10 days
3 yr after dialysis
+++
NA
UVB/No follow-up
No dialysis
+++
NA
Topical cleansing/Cleared in 6 wk
No dialysis
+
Yes
Topical steroids/No follow-up
No dialysis
+
Yes
Removed by biopsy
5 mo after dialysis
+++
Yes
Cleared 6 wk after UYB
8 yr after dialysis
++
NA
UVB/Improved
2 mo after dialysis
2 yr after dialysis
UVB, retinoic acid/Improved Retinoic acid/Resolved in 18 rno NA NA
578 Faver et al.
Journal of the American Academy of Dermatology April 1994
Fig. 1. MUltiple, randomly scattered prurigo-like papules on buttocks and lower part of back. Note Koebner phenomenon from scratching. Fig. 2. Hyperkeratotic umbilicated papules on extensor surface of knee.
eluding our six cases. Of the 22 patients, 11 were men and 11 were women. Their ages at the time of initial examination ranged from 35 to 80 years (mean, 56 years). Nine were white, eight were black, two were Hispanic, and one was Asian; race was not reported for the two others .? Sixteen patients (72%) had associated diabetes mellitus with at least one of its complications (nephropathy, retinopathy, peripheral vascular disease, or cardiomyopathy). Fifteen patients (68%) had some form of nephropathy of various causes (diabetes mellitus, HIV infection , heroin abuse, or glomerulonephritis). Three patients had hypothyroidism, and one had hyperparathyroidism. Two patients had Hodgkin's disease, and one had mixed histiocyticlymphocytic lymphoma. Two patients had some form of liver dysfunction (chronic active hepatitis , liver cirrhosis, or ascites), and three had hypertension. Of the 15 patients who had nephropathy, 10 required dialysis (peritoneal dialysis in one and hemodialysis in nine) . The lesions appeared simultaneously with dialysis in one patient, before dialysis in one, and from 2 months to 8 years after the initiation of dialysis in eight patients. The lesions were distributed mostly on the extensor surfaces of the upper extremities in 17 patients
(77%) and the lower extremities in 15 (68%). The trunk was involvedin 14patients (64%) and the face and scalp in five. Twenty-one patients had mild to severe pruritus. Distribution of the lesionswas linear (Koebner phenomenon) in 13 patients. Treatment was reported in 14 patients. Follow-up data were available for 11 patients. Three patients improved in 6 to 12 weeks with UVB alone, one with retinoic acid alone, and two with both (one of whom had clearing in 18 months). One patient each had clearing with the following treatments: diabetes control, topical cleansing, and punch biopsy removal of a solitary lesion. The histologic features of our six cases were characterized by a dome-shaped lesion with a central crater that extended from the epidermis to the reticular dermis and contained parakeratotic horny material , neutrophils, basophilic granular debris, and degenerated collagen in vertical strands (Fig. 3). The epidermis adjacent to the crater was hyperplastic, thin near the base of the crater, and completely absent at its base where the collagen was extruded. Dense accumulation of neutrophils, lymphocytes, histiocytes, and cellular debris was found where the dermis was in direct contact with the contents of the crater. Masson's trichrome and hematoxylin-eosin
Journal of the American Academy of Dermatology Volume 3D, Number 4
Faver et al. 579
Fig. 3. Keratotic plug containing basophilic debris and collagen, with perforation of epidermis. (Hematoxylin-eosin stain; X 13.) Fig. 4. Dermalcollagen perforating through epidermis. Col1agen bundles are stained blue. (Masson's trichrome stain; XS.)
stains revealed collagen within the epithelium-lined crater. Most collagen bundles were degenerated and fragmented but still blue with Masson's trichrome stain (Fig. 4). Elastic tissue stain failed to reveal elastic fibers within the crater. DISCUSSION RPC, described in 1967 by Mehregan et a1., I is one of four diseases that have been considered the essential perforating disorders: elastosis perforans serpiginosa, RPC, perforating folliculitis, and Kyrle's disease.I3 The disease has two distinct forms: inherited and acquired. In the inherited, or childhood, form, the lesions appear early in life, mainly on exposed surfaces. A genetic predisposition for this type has been suggested. I, 14-1 6 A positive family history is found in at least two thirds of patients. The male-to-female ratio is 2:1.In contrast, the acquired, or adult, form of RPC appears in adulthood , is not familial, and usually is accompanied by scratching. There seems to be no predilection to sex or race, as evident from our review. In both forms the cutaneous lesions usually are multiple, recurrent, umbilicated, hyperpigmented papules and nodules with a central adherent keratotic plug that may resolve spontaneously in 6 to 8 weeks. The lesions are
located mostly on the extensor surfaces of the extremities and on areas that can be reached by the hands. The disease is reported in association with diabetes mellitus or its complications (retinopathy, peripheral vascular disease, or cardiomyopathy), chronic kidney failure with or without dialysis,4-6, 8,9, II, 12lymphomas, 7, II and AIDS. 10 We are the first to report an association of acquired RPC with hypothyroidism, hyperparathyroidism, neurodermatitis, and liver dysfunction. The condition is being recognized more frequently, perhaps because patients with kidney failure and diabetes mellitus are living longer.P The pathogenesis of RPC is unknown. Mehregan et aLI, 17 originally postulated that mild superficial trauma in genetically susceptible persons leads to necrobiosis of the collagen in the dermal papillae, which is subsequently eliminated from the dermis by means of "transepithelial elimination." Other investigators considered trauma an insufficient etiologic factor for the development of the lesions. Cochran et aI. 5 suggested that diabetic vasculopathy accompanied by trauma from scratching caused by diabetes and renal insufficiency may be the underlying factor in this condition, but this theory cannot
580
Faver et al.
explain the occurrence of the disease in nondiabetic patients. Pruritus was present in all described patients. This is the most common cutaneous symptom of chronic kidney failure (15% to 49% of patients), and it can first appear during dialysis, although it may disappear after iL I8 Pruritus can also occur with diabetes mellitus, lymphomas, hyperparathyroidism, and hypothyroidism.'? The linear distribution of some of the lesions, the reproducibility ofRPC by superficial scratching.v '" and the association with acne and insect bite support the theory of superficial trauma. Different treatments have been used for this condition (Table I). The correlation was clear between control of pruritus to prevent scratching and the clearing of the lesions in all described patients. From our experience and review of the literature, we propose the following diagnostic criteria for the adult (acquired) form of RPC: (1) histopathologic findings of elimination of necrotic basophilic collagen bundles into a cup-shaped epidermal depression, (2) clinical lesions of umbilicated papule or nodule with a central, adherent keratotic plug, and (3) onset of the lesions after age 18 years. We believe that acquired RPC is a reaction to superficial trauma caused by scratching in association with many pruritic diseases. The cutaneous lesions usually heal when patients are protected from scratching and their underlying disease is controlled. The presence of the collagen bundles in the crater with the other characteristic pathologic findings helps to differentiate RPC from the other perforating disorders. 20 REFERENCES I. Mehregan AI-I, Schwartz OD, Livingood CS. Reactive perforating collagenosis. Arch Dermatol 1967;96:277-82. 2. Mehregan AH. Elastosis perforans serpiginosa: a review of the literature and report of 11 cases. Arch Dermatol 1968;97:381-93.
Journal of the American Academy of Dermatology April 1994
3. Bovenmyer DA. Reactive perforating collagenosis: experimental production of the lesion. Arch Dermatol 1970; 102:313-7. 4. Poliak SC, Lebwohl MG, Parris A, et a!. Reactive perforating collagenosis associated with diabetes mellitus. N Eng1 J Moo 1982;306:81-4. 5. Cochran RJ, Tucker SB, Wilkin JK. Reactive perforating collagenosis of diabetes mellitus and renal failure. Cutis 1983;31 :55-8. 6. Panzini H, Dore N. L'association de diabete mellitus, d'insuffisance renale chronique et de collagenase perforante reactionnele: apropos d'une observation. Union Med Can 1985;114:411-4. 7. Pedragosa R, Knobel HJ, Huguet P, et al. Reactive perforating collagenosis in Hodgkin's disease. Am J Dermatopathol1987;9:41-4. 8. Vion B, Frenk E. Erworbene reaktive Kollagenose des Erwachsenen: erfolgreiche Behandlung durch UV-B-Lich. Hautarzt 1989;40:448-50. 9. Berger RS. Reactive perforating collagenosis of renal failure/diabetes responsive to topical retinoic acid. Cutis 1989;43:540-2. 10. Bank DE, Cohen PR, Kohn SR. Reactive perforating collagenosis in a setting of double disaster: acquired immunodeficiency syndrome and end-stage renal disease. J AM ACAD DERMATOL 1989;21:371-4. 11. Henry JC, Jorizzo JL, Apisarnthanarax P. Reactive perforating collagenosis in the setting of prurigo nodularis. Int J Dcrmatol1983;22:386-7. 12. Cohen RW, Auerbach R. Acquired reactive perforating collagenosis. J AM ACAD DERMATOL 1989;20:287-9. 13. Patterson JW. The perforating disorders. J AM ACAD DERMATOL 1984;10:561-81. 14. Nair BKH, Sarojini PA, Basheer AM, et a!. Reactive perforating collagenosis. Br J Dermatol 1974;91:399-403. 15. Rotta O. Reactive perforating collagenosis: report of 3 cases. Dermatologica 1983;166:308-10. 16. Kanan MW. Familial reactive perforating collagenosis and intolerance to cold. Br J Dermatol 1974;91:405-14. 17. Nyfors A, Mehregan AH. Reactive perforating collagenosis (Mehregan): report of two new cases and review of literature. Acta Derm Venereol (Stockh) 1973;53:375-80. 18. Gupta AK, Gupta MA, Cardella CJ, et a!. Cutaneous association of chronic renal failure and dialysis. Int J Dermatol 1986;25:498-504. 19. Denman ST. A review of pruritus. JAM ACAD DERMATOL 1986;14:375-92. 20. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott, 1990:301.
Rochester, Minnesota Background: Reactive perforating collagenosis (RPC) is characterized by transepithelial
elimination of altered collagen. Two types havebeen recognized: the childhood form and the adult form. Objective: Our purpose was to review the associated disorders, evaluate the possible causes, and set criteria for the diagnosis of the disease. Methods: The clinicaland pathologicfindings of six patients with the adult form of RPC are reviewed. The literature on this subject is compared with our findings. Results: Pruritus was reported in all cases.Treatment of pruritus cleared the lesions in many patients.This is the first report of an association between RPC and hyperparathyroidism, hypothyroidism, liver disorders, and neurodermatitis. Conclusion: Variousdisorders can be associatedwith the adult form of RPC. Pruritus is the common factor among all types. Control of itching might be helpful for clearing the lesions. We proposethe following diagnosticcriteria for acquired RPC: (1) histopathologic findings of elimination of necrotic basophilic collagen tissueinto a cup-shaped epidermal depression, (2) clinicalpresentation of umbilicated papules or nodules with a central adherent keratotic plug, and (3) onset of skin lesions after the age of 18 years. (J AM ACAD DERMATOL 1994;30:575-80.)
Reactive perforating collagenosis (RPC) is an uncommon condition described in 1967 by Mehregan et a1. 1 as a disease in which altered collagen bundles are eliminated through the epidermis. RPC occurs in two forms: childhood or inherited form, and adult or acquired form. Both forms are believed to be a cutaneous response to superficial trauma.v 3 We describe six patients with the adult (acquired) form ofRPC, reviewthe literature, and compare the clinical features, pathologic findings, associated disorders, and treatment of all published cases. METHODS We identified six patients with a diagnosis of the adult form of RPC at the Mayo Clinic between 1983 and 1992. Charts were reviewed for clinical data. All tissue specimens were obtained by punch biopsy, fixed in 10%
From the Department ofDermatology, Mayo Clinic and Mayo Foundation, Rochester, Minn. Dr. Faver isa visiting clinician at the Department ofDermatology. Accepted for publication Sept. 20, 1993. Reprint requests: W. P. Daniel Su, MD, Department ofDermatology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Copyright @ 1994 by the American Academy ofDermatology, Inc. 0190-9622/94 $3.00 + 0 16/1/51556
formalin, step-sectioned, and stained with hematoxylin and eosin, Schmidt's elastic-Giemsa, and Masson's trichrome stains.The literature on perforating collagenosis was reviewed. CASE REPORT A 43-year-old white man was seen in November 1988 for generalized pruritus that started after he began peritoneal dialysis in July 1984 for chronic kidney failure. He also noticed increased pigmentation and dryness of his skin.Treatment with antihistamines and topical moisturizers produced a limited response. Hemodialysis was started in June 1988, and the patient noticed increasing intensity of his itching associated with an eruption of small papules. Examination revealed multiple linear prurigo-like papules (Fig. 1) with a keratotic central plug (Fig. 2) on the arms, posterior aspect of the scalp, trunk, thighs, and buttocks. The biopsyspecimen wasconsistent with RPC. The patient was treated with topical steroids and wet dressings; 80% improvement was achieved and treatment with UVB was started. The patient was free of RPC within 6 weeks. RESULTS
Table I summarizes the clinical features of all cases that we regard as fulfilling the criteria for the adult (acquired) form of RPC in the literature, in-
575
576
Journal of the American Academy of Dermatology April 1994
Faver et al.
Case
Associated disorders
(author)
1 (Poliak et a1.4)
41/F/B
2
51/F/B
3
80/M/B
4
57/F/H
5
77/M/H
6
65/M/B
7 (Cochran et al. 5) 8
41/F/B 36JF/B
9 (Panzini and Dore6)
56/F/W
10 (Pedragosa et a1. 7)
49/F
11
43/M
12 (Vion and Frenk'')
77/M/W
13 (Berger")
53/M/B
14 (Bank et a1. IO)
38/M/B
15 (Henry et aLII)
35/F/A
16 (Cohen and Auerbach 12)
79/M/W
DM, retinopathy, nephropathy, PVD DM, retinopathy, nephropathy, PVD DM, retinopathy, nephropathy, PVD DM, retinopathy, nephropathy, PVD DM, retinopathy DM, retinopathy, nephropathy, PVD IDDM, retinopathy, nephropathy IDDM, nephropathy IDDM, retinopathy, COPD, HTN, nephropathy, cardiomyopathy, PVD Hodgkin's disease (nodular sclerosis type) Hodgkin's disease (nodular sclerosis type) NIDDM, nephropathy, vitiligo NIDDM, nephropathy, PVD AIDS, HIV, or heroin nephropathy Mixed histiocytic-lymphocytic lymphoma NIDDM, retinopathy
Distribution
Extensor surfaces of extremities Trunk, forehead, extensor surfaces of extremities Trunk, face , extensor surfaces of extremities Trunk, extensor surfaces of extremities Trunk, extensor surfaces of extremities Extensor surfaces of extremities Knees , arms, trunk Upper part of back, extensor surfaces of arms Upper limbs, lower part of back
Predominantly on legs Trunk, abdomen, upper limbs Legs, lower abdomen Chest, arms, legs, dorsum of both feet Extensor surfaces of forearms Arms, legs. back
Presen t cases
17
71/M/W
18
63/F/W
19
54/F/W
20
66/M/W
21
43/M/W
22
56/F/W
Nephropathy, cardiomyopathy, liver dysfunction, ascites, anemia, hyperparathyroidism, PVD, COPD Chronic pruritus ani, anal fissure, neurodermatitis, hypothyroidism, HTN Chronic active hepatitis, liver cirrhosis, NIDDM NIDDM, mild kidney failure, hypothyroidism, PVD Glomerulonephritis, CRF, mild NIDDM, obesity , pericardial tamponade, chronic anemia NIDDM, nephropathy, retinopathy, anemia, hypothyroidism, hyperlipidemia. CAD, HTN
Arms, legs
Buttocks, back , scalp
Dorsal forearms, hands. upper part of back One lesion on eyebrow Arms, posterior scalp, trunk, thighs, buttocks Arms, legs, trunk
+, Mild; ++. moderate; +++, severe; A , Asian; B, black; CAD, coronaryartery disease; C-MOPP, cyclophosphamide, nitrogen mustard, vincristine, prednisone.and procarbazine; COPD, chronic obstructive pulmonarydisease; CRF, chronicrenal failure; DM, diabetes mellitus; DTIC, dacarbazine; H, H ispanic; HTN, hypertension; lDDA-f, insulin-dependent diabetes mellitus; NA , not available; NlDDM, non-insulin-dependent diabetesmellitus; PVD, peripheral vascular disease; UVB, ultraviolet light B; W, white,
Journal of the American Academy of Dermatology Volume 30, Number 4
Relation to dialysis
Faver et al. 577
Pruritus
Koebner phenomenon
Treatment/Improvement
++
Yes
NA
No dialysis
+++
Yes
NA
I yr before dialysis
+++
Yes
NA
No dialysis
+++
Yes
NA
No dialysis
+++
Yes
NA
++
Yes
NA
Few mo after dialysis 2 yr after dialysis
+++ +++
Yes Yes
UVB/Resolved in 3 mo UVB/Undergoing treatment
No dialysis
+++
No
Retinoic acid/improved
No dialysis
NA
NA
No dialysis
+++
NA
Doxorubicin, bleomycin, DTIC, vinblastine/No improvement C-MOPP/deared in 6 rno
Simultaneously with dialysis
+++ +
Yes NA
5 mo after dialysis
+++
NA
No dialysis
++
Yes
No dialysis
+++
Yes
Diabetes control/Resolved in 10 days
3 yr after dialysis
+++
NA
UVB/No follow-up
No dialysis
+++
NA
Topical cleansing/Cleared in 6 wk
No dialysis
+
Yes
Topical steroids/No follow-up
No dialysis
+
Yes
Removed by biopsy
5 mo after dialysis
+++
Yes
Cleared 6 wk after UYB
8 yr after dialysis
++
NA
UVB/Improved
2 mo after dialysis
2 yr after dialysis
UVB, retinoic acid/Improved Retinoic acid/Resolved in 18 rno NA NA
578 Faver et al.
Journal of the American Academy of Dermatology April 1994
Fig. 1. MUltiple, randomly scattered prurigo-like papules on buttocks and lower part of back. Note Koebner phenomenon from scratching. Fig. 2. Hyperkeratotic umbilicated papules on extensor surface of knee.
eluding our six cases. Of the 22 patients, 11 were men and 11 were women. Their ages at the time of initial examination ranged from 35 to 80 years (mean, 56 years). Nine were white, eight were black, two were Hispanic, and one was Asian; race was not reported for the two others .? Sixteen patients (72%) had associated diabetes mellitus with at least one of its complications (nephropathy, retinopathy, peripheral vascular disease, or cardiomyopathy). Fifteen patients (68%) had some form of nephropathy of various causes (diabetes mellitus, HIV infection , heroin abuse, or glomerulonephritis). Three patients had hypothyroidism, and one had hyperparathyroidism. Two patients had Hodgkin's disease, and one had mixed histiocyticlymphocytic lymphoma. Two patients had some form of liver dysfunction (chronic active hepatitis , liver cirrhosis, or ascites), and three had hypertension. Of the 15 patients who had nephropathy, 10 required dialysis (peritoneal dialysis in one and hemodialysis in nine) . The lesions appeared simultaneously with dialysis in one patient, before dialysis in one, and from 2 months to 8 years after the initiation of dialysis in eight patients. The lesions were distributed mostly on the extensor surfaces of the upper extremities in 17 patients
(77%) and the lower extremities in 15 (68%). The trunk was involvedin 14patients (64%) and the face and scalp in five. Twenty-one patients had mild to severe pruritus. Distribution of the lesionswas linear (Koebner phenomenon) in 13 patients. Treatment was reported in 14 patients. Follow-up data were available for 11 patients. Three patients improved in 6 to 12 weeks with UVB alone, one with retinoic acid alone, and two with both (one of whom had clearing in 18 months). One patient each had clearing with the following treatments: diabetes control, topical cleansing, and punch biopsy removal of a solitary lesion. The histologic features of our six cases were characterized by a dome-shaped lesion with a central crater that extended from the epidermis to the reticular dermis and contained parakeratotic horny material , neutrophils, basophilic granular debris, and degenerated collagen in vertical strands (Fig. 3). The epidermis adjacent to the crater was hyperplastic, thin near the base of the crater, and completely absent at its base where the collagen was extruded. Dense accumulation of neutrophils, lymphocytes, histiocytes, and cellular debris was found where the dermis was in direct contact with the contents of the crater. Masson's trichrome and hematoxylin-eosin
Journal of the American Academy of Dermatology Volume 3D, Number 4
Faver et al. 579
Fig. 3. Keratotic plug containing basophilic debris and collagen, with perforation of epidermis. (Hematoxylin-eosin stain; X 13.) Fig. 4. Dermalcollagen perforating through epidermis. Col1agen bundles are stained blue. (Masson's trichrome stain; XS.)
stains revealed collagen within the epithelium-lined crater. Most collagen bundles were degenerated and fragmented but still blue with Masson's trichrome stain (Fig. 4). Elastic tissue stain failed to reveal elastic fibers within the crater. DISCUSSION RPC, described in 1967 by Mehregan et a1., I is one of four diseases that have been considered the essential perforating disorders: elastosis perforans serpiginosa, RPC, perforating folliculitis, and Kyrle's disease.I3 The disease has two distinct forms: inherited and acquired. In the inherited, or childhood, form, the lesions appear early in life, mainly on exposed surfaces. A genetic predisposition for this type has been suggested. I, 14-1 6 A positive family history is found in at least two thirds of patients. The male-to-female ratio is 2:1.In contrast, the acquired, or adult, form of RPC appears in adulthood , is not familial, and usually is accompanied by scratching. There seems to be no predilection to sex or race, as evident from our review. In both forms the cutaneous lesions usually are multiple, recurrent, umbilicated, hyperpigmented papules and nodules with a central adherent keratotic plug that may resolve spontaneously in 6 to 8 weeks. The lesions are
located mostly on the extensor surfaces of the extremities and on areas that can be reached by the hands. The disease is reported in association with diabetes mellitus or its complications (retinopathy, peripheral vascular disease, or cardiomyopathy), chronic kidney failure with or without dialysis,4-6, 8,9, II, 12lymphomas, 7, II and AIDS. 10 We are the first to report an association of acquired RPC with hypothyroidism, hyperparathyroidism, neurodermatitis, and liver dysfunction. The condition is being recognized more frequently, perhaps because patients with kidney failure and diabetes mellitus are living longer.P The pathogenesis of RPC is unknown. Mehregan et aLI, 17 originally postulated that mild superficial trauma in genetically susceptible persons leads to necrobiosis of the collagen in the dermal papillae, which is subsequently eliminated from the dermis by means of "transepithelial elimination." Other investigators considered trauma an insufficient etiologic factor for the development of the lesions. Cochran et aI. 5 suggested that diabetic vasculopathy accompanied by trauma from scratching caused by diabetes and renal insufficiency may be the underlying factor in this condition, but this theory cannot
580
Faver et al.
explain the occurrence of the disease in nondiabetic patients. Pruritus was present in all described patients. This is the most common cutaneous symptom of chronic kidney failure (15% to 49% of patients), and it can first appear during dialysis, although it may disappear after iL I8 Pruritus can also occur with diabetes mellitus, lymphomas, hyperparathyroidism, and hypothyroidism.'? The linear distribution of some of the lesions, the reproducibility ofRPC by superficial scratching.v '" and the association with acne and insect bite support the theory of superficial trauma. Different treatments have been used for this condition (Table I). The correlation was clear between control of pruritus to prevent scratching and the clearing of the lesions in all described patients. From our experience and review of the literature, we propose the following diagnostic criteria for the adult (acquired) form of RPC: (1) histopathologic findings of elimination of necrotic basophilic collagen bundles into a cup-shaped epidermal depression, (2) clinical lesions of umbilicated papule or nodule with a central, adherent keratotic plug, and (3) onset of the lesions after age 18 years. We believe that acquired RPC is a reaction to superficial trauma caused by scratching in association with many pruritic diseases. The cutaneous lesions usually heal when patients are protected from scratching and their underlying disease is controlled. The presence of the collagen bundles in the crater with the other characteristic pathologic findings helps to differentiate RPC from the other perforating disorders. 20 REFERENCES I. Mehregan AI-I, Schwartz OD, Livingood CS. Reactive perforating collagenosis. Arch Dermatol 1967;96:277-82. 2. Mehregan AH. Elastosis perforans serpiginosa: a review of the literature and report of 11 cases. Arch Dermatol 1968;97:381-93.
Journal of the American Academy of Dermatology April 1994
3. Bovenmyer DA. Reactive perforating collagenosis: experimental production of the lesion. Arch Dermatol 1970; 102:313-7. 4. Poliak SC, Lebwohl MG, Parris A, et a!. Reactive perforating collagenosis associated with diabetes mellitus. N Eng1 J Moo 1982;306:81-4. 5. Cochran RJ, Tucker SB, Wilkin JK. Reactive perforating collagenosis of diabetes mellitus and renal failure. Cutis 1983;31 :55-8. 6. Panzini H, Dore N. L'association de diabete mellitus, d'insuffisance renale chronique et de collagenase perforante reactionnele: apropos d'une observation. Union Med Can 1985;114:411-4. 7. Pedragosa R, Knobel HJ, Huguet P, et al. Reactive perforating collagenosis in Hodgkin's disease. Am J Dermatopathol1987;9:41-4. 8. Vion B, Frenk E. Erworbene reaktive Kollagenose des Erwachsenen: erfolgreiche Behandlung durch UV-B-Lich. Hautarzt 1989;40:448-50. 9. Berger RS. Reactive perforating collagenosis of renal failure/diabetes responsive to topical retinoic acid. Cutis 1989;43:540-2. 10. Bank DE, Cohen PR, Kohn SR. Reactive perforating collagenosis in a setting of double disaster: acquired immunodeficiency syndrome and end-stage renal disease. J AM ACAD DERMATOL 1989;21:371-4. 11. Henry JC, Jorizzo JL, Apisarnthanarax P. Reactive perforating collagenosis in the setting of prurigo nodularis. Int J Dcrmatol1983;22:386-7. 12. Cohen RW, Auerbach R. Acquired reactive perforating collagenosis. J AM ACAD DERMATOL 1989;20:287-9. 13. Patterson JW. The perforating disorders. J AM ACAD DERMATOL 1984;10:561-81. 14. Nair BKH, Sarojini PA, Basheer AM, et a!. Reactive perforating collagenosis. Br J Dermatol 1974;91:399-403. 15. Rotta O. Reactive perforating collagenosis: report of 3 cases. Dermatologica 1983;166:308-10. 16. Kanan MW. Familial reactive perforating collagenosis and intolerance to cold. Br J Dermatol 1974;91:405-14. 17. Nyfors A, Mehregan AH. Reactive perforating collagenosis (Mehregan): report of two new cases and review of literature. Acta Derm Venereol (Stockh) 1973;53:375-80. 18. Gupta AK, Gupta MA, Cardella CJ, et a!. Cutaneous association of chronic renal failure and dialysis. Int J Dermatol 1986;25:498-504. 19. Denman ST. A review of pruritus. JAM ACAD DERMATOL 1986;14:375-92. 20. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott, 1990:301.