Familial Cutaneous Collagenoma

Authors

  • Marianne E. Dawn MD,

    1. From the Department of Dermatology, University of Maryland School of Medicine, Baltimore,1 and Comparative Pathology, United States Army Medical Research Institute of Chemical Defense,2 Aberdeen Proving Ground, Aberdeen, MD
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  • 1 April C. Deng MD, PhD,

    1. From the Department of Dermatology, University of Maryland School of Medicine, Baltimore,1 and Comparative Pathology, United States Army Medical Research Institute of Chemical Defense,2 Aberdeen Proving Ground, Aberdeen, MD
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  • 1 John Petrali PhD,

    1. From the Department of Dermatology, University of Maryland School of Medicine, Baltimore,1 and Comparative Pathology, United States Army Medical Research Institute of Chemical Defense,2 Aberdeen Proving Ground, Aberdeen, MD
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  • 2 Caroline Wessely BS,

    1. From the Department of Dermatology, University of Maryland School of Medicine, Baltimore,1 and Comparative Pathology, United States Army Medical Research Institute of Chemical Defense,2 Aberdeen Proving Ground, Aberdeen, MD
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  • 2 David Jaffe MD,

    1. From the Department of Dermatology, University of Maryland School of Medicine, Baltimore,1 and Comparative Pathology, United States Army Medical Research Institute of Chemical Defense,2 Aberdeen Proving Ground, Aberdeen, MD
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  • and 1 Anthony A. Gaspari MD 1

    1. From the Department of Dermatology, University of Maryland School of Medicine, Baltimore,1 and Comparative Pathology, United States Army Medical Research Institute of Chemical Defense,2 Aberdeen Proving Ground, Aberdeen, MD
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Marianne E. Dawn, MD, Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, 6th Floor, Baltimore, MD 21201
E-mail: marianne.dawn@gmail.com

Abstract

A 41-year-old woman presented to our dermatology clinic in February 2005 with a chief complaint of numerous flesh-colored nodules on her back and abdomen. She initially noticed the lesions at age 17 years. The plaques had increased in size and number over time, but remained asymptomatic. The patient reported multiple similar lesions on a maternal uncle and a cousin. Her family history was also notable for cardiomyopathy, resulting in the death of her mother. The patient's past medical history was notable for poorly controlled type I diabetes, currently managed with an insulin pump; and coronary artery disease. The patient had undergone multiple cardiac procedures before the age of 40 years, including quadruple coronary artery bypass grafting surgery and placement of 9 cardiac stents. Her ejection fraction on cardiac catheterization in November 2004 was 65% with no wall motion abnormalities. On physical examination, numerous spongy, discrete, flesh-colored plaques and nodules were seen concentrated across the upper part of her back between the scapulae as well as underneath the breasts and across the flanks (Figure 1). All lesions were asymptomatic. Prior workup of this patient had included plain films of the long bones and hands, which were within normal limits. A biopsy from lesional skin on the back highlighted by trichome stain showed an increased number of markedly thickened and eosinophilic dermal collagen bundles compared with adjacent normal skin. Immunohistochemical studies with anticollagen type I and type III antibodies confirmed that the increased collagen material consisted of type I collagen fibers, which is the same type of collagen found in normal dermis. The elastic fibers, highlighted by Verhoeff-van Gieson stain (Figure 2), were diminished and haphazardly arranged. No increased cellular component or inflammatory infiltrate was observed. These findings were consistent with a collagenoma. Further analysis of the lesional tissue by electron microscopy revealed that the ultrastructural appearance of the collagen fibers, including arrangement and diameters, were not significantly different from that of the normal tissue (Figure 3).

Figure 1.

On physical examination, numerous spongy, flesh-colored plaques and nodules were seen concentrated across the upper part of the patient's back between the scapulae.

Figure 2.

Elastic stain of lesional tissue demonstrates a diminished number of abnormal elastic fibers intermingled with thickened collagen bundles; Verhoeff-van Gieson stain, original magnification ×40.

Figure 3.

On electron microscopy, the ultrastructural appearance of the collagen fibers, including arrangement and diameters, was not significantly different from that of the normal tissue.

Familial cutaneous collagenoma is a rare autosomal dominant condition characterized by multiple collagenomas appearing on the trunk after puberty. This condition has a possible association with cardiovascular disease and must be distinguished from several other diseases in which collagenomas may be found.

Collagenomas are uncommon connective tissue nevi in which dense collagen bundles are found in the dermis. Multiple collagenomas are a component of several diseases and syndromes, including Buschke-Ollendorf syndrome, tuberous sclerosis, eruptive collagenomas, and familial cutaneous collagenoma.

Buschke-Ollendorf syndrome is inherited in an autosomal dominant fashion and is characterized by the features of dermatofibrosis lenticularis disseminata and osteopoikilosis. The expression of these features may be variable. Osteopoikilosis is the finding of 1-to-10-mm well-circumscribed, benign, sclerotic densities in the ends of long bones, the pelvis, and the hands.1 These asymptomatic densities may be demonstrated by plain films, which were normal in the case of the current patient. The cutaneous lesions in Buschke-Ollendorf syndrome, dermatofibrosis lenticularis disseminata, are most often elastic connective tissue nevi, but collagenomas may also be present. These lesions have a predilection for the lower part of the trunk, arms, and buttocks and most often initially appear in childhood.2 The distribution and age of onset of the collagenomas as well as the normal plain films of the hands, pelvis, and long bones in the present patient are inconsistent with a diagnosis of Buschke-Ollendorf syndrome.

Tuberous sclerosis, an autosomal dominant neurocutaneous disease, is characterized by cutaneous and internal hamartomas including the shagreen patch. These connective tissue nevi are typically single, yellow, irregular plaques with a leathery surface that are found on the lower part of the back. Thus, the clinical presentation easily distinguishes these collagenomas from the lesions seen in familial cutaneous collagenoma. Diagnosis of tuberous sclerosis is further facilitated by the finding of other characteristic cutaneous lesions including facial angiofibromas, ash-leaf macules, periungual fibromas, and confetti-like macules.3

Eruptive collagenoma cases may present in an identical fashion to cases of familial cutaneous collagenoma but lack evidence of inheritance or associated systemic findings. The lesions of eruptive collagenoma appear in the first or second decades as cutaneous nodules and papules distributed on the lower trunk and extremities.4 While lesions typically appear in the preadolescent period, cases of eruptive collagenomas in early adulthood have been reported, as well as a case during pregnancy.5 Familial cutaneous collagenoma has never been reported to initially present during pregnancy; however, 2 women have been described to have experienced an increase in the number of lesions during pregnancy.6 These cases raise the question as to whether the growth of collagenomas in eruptive collagenoma or familial cutaneous collagenoma may be influenced by hormonal factors. The patient we describe here has never been pregnant but did initially develop collagenomas following puberty.

Familial cutaneous collagenoma is an autosomal dominant condition, first described in 1968. Six families, including a total of 18 affected individuals, have been reported in the literature.6–11 The typical presentation is the development of asymptomatic cutaneous nodules, symmetrically distributed over the upper part of the trunk and mid back, with onset after puberty (Table). The patient described in this report and her family are the seventh known family with familial cutaneous collagenoma.

Table Table.  Features of familial cutaneous collagenoma
Inheritance patternAutosomal dominant
Age of onsetPuberty
Cutaneous findingsAsymptomatic cutaneous nodules, symmetrically distributed over the upper part of the trunk and back
Possible associationsCardiac disease
Treatment optionsSurgical excision or intralesional steroid injection of cutaneous lesions

Of interest, 4 of the 18 described patients diagnosed with familial cutaneous collagenoma have also had cardiomyopathy, 2 have had conduction abnormalities, 1 has had coronary artery disease, and 3 have had hypertension. These comorbidities have led several authors to believe that there may be an association with underlying cardiac disease, possibly due to fibrosis of heart structures and blood vessel walls.6

This patient exprienced advanced cardiovascular disease from a young age and has a family history of cardiomyopathy. While her severe cardiovascular disease can be explained by the presence of diabetes, collagen deposition in the vascular walls is a possible accelerating factor in the rapid progression of her heart disease. A cardiac biopsy would be required to document collagen deposition in the myocardium and blood vessel walls.

Treatment of the cutaneous manifestations of this patient's disease has included surgery and intralesional steroid injections. Collagenomas in locations that caused irritation to the patient were excised without recurrence; however, new collagenomas have continued to develop at other sites. Several lesions have also been injected with triamcinolone acetonide, with marked reduction in size. Use of intralesional steroids is a promising therapeutic approach for problematic collagenomas.

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