Dermatology Online Journal

Generalized eruptive keratoacanthomas of Grzybowski
Phoebe D Lu MD PhD, Arnold Lee MD PhD, Christopher T Cassetty MD, Wang Cheung MD, Nadia Wang MD, Allan C Halpern MD, David E Cohen MD MPH
Dermatology Online Journal 15 (8): 6

Department of Dermatology, New York University

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Abstract

A 48-year-old man presented with a two-year history of a generalized, pruritic eruption that was associated with numerous, dome-shaped papules and nodulocystic lesions. Biopsy specimens have shown keratoacanthomas and a lichenoid dermatitis. Evaluation for malignant conditions has been negative. Owing to the constellation of findings, a diagnosis of generalized eruptive keratoacanthomas of Grzybowski associated with lichenoid dermatitis and acneiform lesions is favored. The patient is currently on a trial of acitretin.

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Figure 1	Figure 2

History

A 48-year-old man presented to the Charles C. Harris Skin and Cancer Pavilion with a two-year history of a pruritic eruption that began on his arms, hands, and chest in October, 2006. He was originally treated for eczematous dermatitis with topical glucocorticoids with minimal improvement. His skin lesions gradually spread to the face, lips, neck, and trunk. In February, 2007, the patient started to develop multiple, discrete papules on the trunk and extremities. Biopsy specimens showed squamous-cell carcinomas and keratoacanthomas. Subsequently, he underwent 33 standard and Mohs micrographic surgical procedures to remove the tumors.

Since then, the patient has undergone an extensive evaluation to rule out a paraneoplastic process. Upper endoscopy showed mild esophagitis with brushings positive for Candida albicans and patchy gastrititis in the antrum, which were treated with fluconazole and esomeprazole. Colonoscopy showed multiple polyps, diverticulosis, and internal hemorrhoids but no evidence of a malignant condition. A bone-marrow biopsy specimen was normocellular with mild eosinophilia, normal trilineage maturation, and increased iron stores. Genetic analysis showed negative mutations for JAK2 and BCR/ABL. Furthermore, computed tomography scans of the chest, abdomen, and pelvis in October, 2007, showed two stable subcentimeter pulmonary nodules in the right lung that were most suggestive of pleural thickening or scars. A positron emission tomography scan was negative.

In 2008, an occupational medicine specialist determined that his skin condition was not due to possible dioxin exposure in the past. An allergist made the diagnoses of allergic rhinitis and asthma. Prick skin tests were positive for pollens, mold, and dog, which were felt not to be relevant. Patch tests to the North American Contact Dermatitis Group standard series were negative.

Past medical history includes hypercholesterolemia. Past dermatologic history includes nodulocystic acne and abscesses in the intertriginous areas for which he was treated with isotretinoin in the past. He denies any allergies to medications. His medications include levocetirizine, esomeprazole, montelukast, and fluoxetine. Family history is non-contributory. The patient lives alone and has worked as a civil engineer since 1978 and spends approximately 50 percent of his time in the office and 50 percent in the field. He has a 25 pack-year history of smoking cigarettes. He denies history of exposure to arsenic or coal tar.

Previous treatments included topical and oral glucocorticoids and antihistamines. The patient exhibited appreciable remission in some of his skin lesions with the use of prednisone up to 60 mg daily. The patient was recently started on acitretin 25 mg daily.

Physical Examination

Multiple, <5 mm, dome-shaped, skin-colored-to-hyperpigmented papules, some of which have central keratinaceous plugs or hyperkeratosis, were present on face, trunk, and upper and lower extremities. Hyperkeratotic scale was noted on the palms. On the left anterior shin were erythematous, thin plaques with fine scale and scattered, overlying dome-shaped papules. Scattered, nodulocystic lesions also were noted on face, chest, and back. Lymphadenopathy was absent.

Laboratory data

A complete blood count, basic metabolic panel, and hepatic panel were normal except for an elevated white-cell count of 14.6 x 10⁹/L. Blood and urine arsenic levels were normal. Anti-nuclear, anti MI-2, anti-Jo-1, hepatitis C, and hepatitis B surface antibodies were negative. Creatine phosphokinase, aldolase, and rapid plasma reagin levels were normal. Immunoglobulins A, G, and M; thyroid function tests; carcinoembryonic antigen, and prostate specific antigen were normal. Antigliadin IgG was mildly elevated but antigliadin IgA was normal. Tissue transglutaminase and anti-endomysial antibodies were negative.

Histopathology

There are endophytic proliferations of squamous cells with pale, eosinophilic cytoplasm and a central crater containing keratin. In some sections, the squamous proliferations are associated with a dense lichenoid inflammation, necrotic keratinocytes, and melanin incontinence.

Comment

Generalized eruptive keratoacanthomas of Grzybowski is a rare condition; approximately 30 cases have been reported in the literature since its first description in the 1950s [1]. It typically affects middle-aged adults in the fifth to seventh decade, with an equal preponderance for men and women. Hundreds of small keratoacanthomas develop abruptly and may persist for several months. Spontaneous regression may occur, which leads to atrophic scars. The mucosal surfaces may be affected as well. Other associated findings include severe pruritus, a Koebner reaction, a mask-like facial appearance, ectropion, and hoarseness due to nodules on the larynx.

Eruptive keratoacanthomas also have have been reported to develop in the context of immunosuppressive therapy [2] and in other familial syndromes. Familial keratoacanthomas of the Ferguson-Smith type is an autosomal dominant condition that arises in children and young adults. These keratoacanthomas are found on sun-exposed areas and spontaneously involute. They can recur after years or decades. As compared to the Ferguson-Smith type, the Grzybowski type exhibits an increased number of widespread, smaller keratoacanthomas and involvement of oral mucosa. Features of both Grzybowski and Ferguson-Smith types are found in the multiple familial keratoacanthoma of Witten and Zak [3]. In addition, Muir-Torre syndrome is a genodermatosis that is associated with keratoacanthomas, sebaceous neoplasms, and gastrointestinal tract malignant condition, most commonly of the colon.

There have been several published case reports of keratocanthomas and infundibulocystic hyperplasia that developed in the context of hypertrophic, lichen planus [4, 5, 6, 7]. In these cases, patients presented with limited skin involvement, mostly on the lower extremities, and not with a generalized distribution. In one case series, the patients responded well to acitretin [7].

Controversy exists as to whether keratoacanthomas are benign lesions that spontaneously regress within four to six months or early forms of squamous-cell carcinomas. Thus, surgical excision of individual lesions is often advocated. Owing to the impracticality of excision for treatment of generalized eruptive keratoacanthoma, a number of local and systemic medications have been used with variable success. These include intralesional 5-fluorouracil, methotrexate, bleomycin, and glucocorticoids [8], systemic retinoids, methotrexate, and cyclophosphamide [9]. Emollients and antihistamines also are used for symptomatic relief. Surgical correction is recommended for patients who develop ectropion.

References

1. Schwartz RA, et al. Generalized eruptive keratoacanthoma of Grzybowski: follow-up of the original description and 50-year retrospect. Dermatology 2002; 205:345 [PubMed]

2. Dessoukey MW, et al. Eruptive keratoacanthomas associated with immunosuppressive therapy in a patient with systemic lupus erythematosus. J Am Acad Dermatol 1997; 37:478 [PubMed]

3. Agarwal M, et al. Multiple familial keratoacanthoma of Witten and Zak-a report of three siblings. Dermatology 1999; 168:396 [PubMed]

4. Badell A, et al. Keratoacanthoma arising in hypertrophic lichen planus. Br J Dermatol 2000; 142:370.[PubMed]

5. Giesecke LM, et al. Giant keratoacanthoma arising in hypertrophic lichen planus. Australas J Dermatol 2003; 44:267 [PubMed]

6. Chave TA, et al. Keratoacanthoma developing in hypertrophic lichen planus. Br J Dermatol 2003; 148:592 [PubMed]

7. Kossard S, et al. Hypertrophic lichen planus-like reactions combined with infundibulocystic hyperplasia: pathway to neoplasia. Arch Derm 2004; 140:1262 [PubMed]

8. Sanders S, et al. Intralesional corticosteroid treatment of multiple eruptive keratoacanthomas: case report and review of a controversial therapy. Derm Surg 2002; 28:954 [PubMed]

9. Oakley A, et al. Grzybowski's generalized eruptive keratoacanthoma: remission with cyclophosphamide. Australas J Dermatol 2005; 46:118 [PubMed]

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