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Acquired perforating dermatosis associated with metastatic colon cancer

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Acquired perforating dermatosis associated with metastatic colon cancer
Hana Jeon AB1, G Peter Sarantopoulos MD2, Nima M Gharavi MD PhD3, Emma Taylor MD3, Melvin W Chiu MD MPH3
Dermatology Online Journal 17 (11): 7

1. David Geffen School of Medicine at UCLA, Los Angeles, California
2. Division of Dermatopathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
3. Division of Dermatology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California


Acquired perforating dermatosis (APD) is a type of perforating disorder that is traditionally thought to be associated with diabetes, chronic renal failure, or occasionally liver disease. We report a case of APD in a patient with stage IV colon cancer with hepatic metastases. Although rare, APD associated with colon cancer is an important entity to consider; APD may be associated with a broader range of systemic diseases than previously recognized.


Acquired perforating dermatosis (APD) is one of the major perforating disorders, characterized by discrete cutaneous papules and nodules consisting of keratotic plugs in which dermal connective tissue perforates and is eliminated through the epidermis [1]. The term APD was first coined by Rapini and colleagues in 1989 when they reported several cases of patients with renal disease or diabetes mellitus that developed perforating dermatoses [2]. Biopsies taken from lesions on these patients showed combined transepidermal elimination of both collagen and elastic fibers. Rapini and colleagues noted that such findings were not characteristically seen in any of the four previously defined perforating diseases — reactive perforating collagenosis, elastosis perforans serpiginosa, perforating folliculitis, and Kyrle disease — and suggested that the process be referred to as “acquired perforating dermatosis.” Since then, APD has largely been considered as an entity that represents perforating diseases occurring in adults with diabetes or chronic renal failure. Acquired perforating dermatosis has also been reported to occur with liver disease [3]. Here, we report a case of APD in a patient with metastatic colon cancer, which has previously rarely been reported.

Case presentation

Figure 1Figure 2
Figure 1. Erythematous, hyperkeratotic, ulcerated papules on the lower extremities

Figure 2. Histologic sections revealed hyperplastic epidermis bordering a central dell/channel containing inflammatory cells, cellular debris and fragmented, coarse elastic fibers (H&E, x200)

A 59-year-old man with stage IV colon cancer and liver metastases presented with a rash on his trunk and extremities. The patient reported that the rash, which was extremely pruritic, was present for three weeks, since the patient began hydrocodone/paracetamol. The patient had also been taking olmesartan daily for hypertension and polyethylene glycol-electrolyte solution (MiraLAX) for constipation for two years. He had been diagnosed with stage IV colon cancer, one month prior, and a recent magnetic resonance cholangiopancreatography had shown metastatic lesions to the liver compressing upon the intrahepatic inferior vena cava. The patient had undergone chemotherapy with capecitabine and oxaliplatin one and a half weeks prior to presentation. On physical examination, erythematous papules were noted on his arms, legs, and abdomen, with multiple notable excoriations (Figure 1). Differential diagnosis included vasculitis, drug-associated eruption, resolving disseminated varicella, and perforating disorder. At the time of his presentation, the white blood cell count was 37,900 per cubic millimeter (mm³) with 85 percent polymorphonuclear leukocytes, hemoglobin 13.9 grams per deciliter, hematocrit 39.9 percent, and platelet 342,000/mm³. The liver function tests revealed an alkaline phosphatase level of 443 units per liter (U/L), alanine aminotransferase of 169 U/L, and aspartate aminotransferase of 306 U/L. Urinalysis was positive for bacteria and leukocyte esterase, but stool and blood cultures were negative. Lipase was 152 U/L, amylase 277 U/L, and carcinoembryonic antigen was 243 micrograms per liter.

Figure 3
Figure 3. (A) High-power view of extruded, coarse elastic fibers amidst inflammation and cellular debris (arrows; H&E, x600). (B) special staining strongly highlights coarse elastic fibers and supports the diagnosis (arrows; Verhoeff-Van Gieson stain/elastic-Van Gieson (EVG), x600)

A punch biopsy of the left leg was performed, which revealed a cup-shaped depression within the epidermis filled with a mixture of acute and chronic inflammatory cells, necrotic debris, and collagen bundles (Figure 2). Collagen bundles were seen to be extruding into the overlying inflammatory lesion, and reactive squamous epithelium was noted at the edges of the cup-shaped ulcer. There was no evidence of vasculitis in the original pathology section and multiple deeper sections examined. No viral inclusions were seen and there was no evidence of malignancy. PAS stain highlighted the presence of collagen bundles within the ulcer. Trichrome and elastic stains were performed on the tissue in an effort to confirm the diagnostic impression of perforating disorder. These special stains showed transepidermal elimination of elastic fibers and collagen fibers within the cup-shaped invagination upon deeper histologic sections, rendering the diagnosis of perforating disorder (Figure 3).


Acquired perforating dermatosis classically presents with pruritic papules and nodules distributed most commonly on areas accessible to scratching, such as the limbs and trunk [1, 2, 4]. In patients with APD, pruritus that leads to chronic scratching is thought to induce trauma in the epithelium and superficial dermis, leading to transepidermal elimination of collagen or elastic fibers [5]. It has also been suggested that alterations in collagen or elastic fibers related to various etiologies, such as metabolic disturbances, or microdeposition of substances, such as calcium salts, might contribute to the pathogenesis [6]. To our knowledge, only one case of APD associated with colon cancer has been reported [7]. It is important to note, however, that our patient did have liver metastases and that other malignancies have also been associated with APD. Aside from colon cancer, acute leukemia [8], hepatocellular carcinoma [9, 10], renal cell carcinoma [4], thyroid cancer [11], prostate cancer [12], and lymphoma [13] have been reported in association with APD. This suggests that APD may encompass a greater range of disease processes than conventionally recognized, and may in some cases represent a paraneoplastic process.

Treatments for APD and perforating diseases have mostly been anecdotal and no well-designed studies exist to evaluate their efficacy [3]. Phototherapy (ultraviolet B or psoralen and ultraviolet A) is favored, especially for patients with renal disease, because the treatment often alleviates the coexisting pruritus. Typical pruritus treatment with antihistamines has been ineffective. Oral or topical retinoids and intralesional corticosteroids have been reported to show some success [6, 14]. Additionally, treating the systemic disease associated with APD, such as renal transplantation for dialysis patients, has been reported to help as well [15].

To the best of our knowledge, APD in association with metastatic colon cancer has only rarely been reported. Clinicians should think of APD not as a disease limited to patients with diabetes or renal disease, but rather as a larger entity of disease that may be associated with other systemic diseases or malignancies such as metastatic colon cancer. More studies need to be performed to elucidate the pathogenesis of APD and to evaluate various methods of treatment.


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