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Dermatology > DISEASES OF THE DERMIS
Elastosis Perforans Serpiginosum
Article Last Updated: Jun 29, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 12  
Author: Elizabeth A Liotta, MD, Assistant Professor, Department of Dermatology, Uniformed Services University of the Health Sciences
Elizabeth A Liotta is a member of the following medical societies: American Academy of Dermatology
Editors: James W Patterson, MD, Director of Dermatopathology, Professor of Pathology and Dermatology, Departments of Pathology and Dermatology, University of Virginia Medical Center; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Rosalie Elenitsas, MD, Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
Author and Editor Disclosure
Synonyms and related keywords:
elastosis intrapapillare, elastoma intrapapillare perforans, elastoma intrapapillare perforans verruciformis, elastosis perforans, elastoma verruciform perforans (Miescher), keratosis follicularis et parafollicularis serpiginosa, keratosis follicularis serpiginosa (Lutz), reactive perforating elastosis
Background
Elastosis perforans serpiginosa (EPS) is a rare skin disease in which abnormal elastic tissue fibers, other connective tissue elements, and cellular debris are expelled from the papillary dermis through the epidermis (transepithelial elimination). EPS may be distinguished morphologically and histologically from other cutaneous diseases. The first recognizable description of EPS was provided by Fischer in 1927 but was offered as an example of Kyrle disease. Jones and Smith also described EPS in 1947 but mistook it for porokeratosis of Mibelli. In 1953, Lutz recognized the features of EPS as those of an unknown disease and termed the condition keratosis follicularis serpiginosa. Miescher believed the condition was unique and termed it elastoma intrapapillare perforans verruciform. EPS is a disease of connective tissue, possibly of autoantigenic etiology, that occurs in the following 3 forms: - Idiopathic EPS: The cause of idiopathic EPS is unknown; genetic predisposition is possible.
- Reactive EPS: This form is associated regularly with systemic, inherited, fibrous tissue abnormalities, such as Down syndrome, Ehlers-Danlos syndrome, Marfan syndrome, osteogenesis imperfecta, scleroderma, and pseudoxanthoma elasticum.
- Drug-induced EPS: This form is caused by the pharmacologic effect of D-penicillamine and occurs in approximately 1% of patients treated with the drug.
Pathophysiology
EPS may be a form of granulomatous inflammation that displays an unusual method for removing elastic tissue from the area of involvement.
Skin responds to threats to its integrity by foreign materials, such as bacteria, parasites, fungi, and misplaced native tissue elements (eg, hair), silica, beryllium, suture materials, through granulomatous inflammation.
The first stage of the granulomatous inflammation is the destruction of normal connective tissue. Then, an attack on the foreign material in the region ensues with waves of phagocytic histiocytes, often clumped into giant cells, moving in to engulf the foreign substances and debris. These phagocytic histiocytes carry away the foreign substances and debris, usually via vascular channels, but in the perforating diseases, via direct extrusion. The repair process follows close behind, with neovascularization and fibrosis. The duration of such a project is highly variable, often taking years to complete.
Frequency
United States
EPS is a rare condition.
International
No geographic preferences are apparent.
Mortality/Morbidity
In most cases, cutaneous EPS is of cosmetic consequence only. A rare systemic version is fatal, in which abnormal elastic tissue is found in the walls of ruptured blood vessels and viscera.
Race
No racial differences have been reported.
Sex
Male-to-female ratio is approximately 4:1.
Age
EPS usually appears during the second decade of life, but it may be seen in early childhood or late in life.
Duration: The disease lasts a few years; however, in those cases associated with Down syndrome, EPS is a more prolonged and generalized eruption.
History
- Small papules erupt and are grouped in a confined area, eventually becoming serpiginous. The central core of each papule contains a compressed aggregate of fibrous material and cellular debris that, eventually, is disgorged to the surface, after which the papule subsides and disappears.
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- EPS usually is asymptomatic but can be pruritic.
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- Secondary lesions are vague scars or areas of roughness and hypopigmentation or hyperpigmentation that result after the primary lesions have subsided and disappeared.
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- Three general categories of EPS are recognized.
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- Idiopathic: Familial groupings have implicated both dominant and recessive types of inheritance. Inciting events are not known. Probably, 65% (or more) of EPS cases are idiopathic.
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- Reactive
- Associated with other diseases (eg, Down syndrome, Ehlers-Danlos syndrome, Marfan syndrome, osteogenesis imperfecta, scleroderma, acrogeria, perforating granuloma annulare, pseudoxanthoma elasticum). More than 1% of people with Down syndrome have EPS.
- Perforating diseases that may occur in conjunction with EPS include reactive perforating collagenosis, perforating folliculitis, and Kyrle disease. Sufficient similarities and overlapping features are seen to suspect them of being variants of EPS in these patients; however, EPS is not associated regularly with diabetes, while the other 3 diseases usually are associated with diabetes. Reactive types comprise 25-30% of cases of EPS.
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- Drug-induced: D-penicillamine appears to be the only drug with which EPS is a side effect. This form of EPS occurs in approximately 1% of treated patients. Usually, long-term treatment for Wilson disease provokes the occasional case of EPS, but its use in the treatment of cystinuria and rheumatoid arthritis has had similar effects. The EPS eruption may appear 1 or more years after the start of treatment. This eruption often is symmetrical, widespread, and long lasting. It may appear at any time after treatment begins and usually resolves after withdrawal of the drug.
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Physical
- Clinical features of EPS
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- Primary lesions are eruptive, dome-shaped, eventually umbilicated papules, measuring a few to several millimeters in diameter.
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- Lesions are flesh colored to red.
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- Usually, lesions are grouped in linear, arciform, circular, or serpiginous patterns, measuring several centimeters in diameter.
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- New papules may appear in lines and figures that appear to migrate and enlarge peripherally.
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- Distribution
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- Any part of the skin may be affected. Most patients have only 1 area of skin involvement at a time, with the exception of Down syndrome patients, who typically have numerous active lesions. Frequently, these patients have symmetric extremity lesions.
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- If multiple lesions are present, the figures may display a degree of anatomic symmetry.
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- Sites: The sites most commonly affected are the nape of the neck (70%), upper extremities (20%), face (11%), lower extremities (6%), and trunk (3%). One case of penile involvement was reported in 2003.
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Causes
- Elastic fibers are perceived by the skin to be abnormal and become the primary objects of an inflammatory attack. They may be abnormal as a result of genetic influence or penicillamine. Genetic abnormality does not explain the sporadic nature of EPS nor its spontaneous disappearance. Obviously, a secondary factor must be required to make elastic fibers provoke their own expulsion.
- In reports and reviews of the disease, the swollen, broken, and deformed elastic fibers always are clumped in the papillary dermis, making transepidermal elimination convenient. This finding suggests that the unknown secondary factor that denatures cutaneous elastic fibers may have its source outside the body.
- Heat, light, or a traumatic event can be at fault.
- In penicillamine-induced cases, proper cross-linkage formation has been observed to occur with the assistance of lysyl oxidase, which is a copper-dependent enzyme.
- Penicillamine is a copper chelator and may interfere with the function of lysyl oxidase and the proper construction of elastic fibers.
Other Problems to be Considered
Dermatophytosis
Perforating collagenosis
Perforating granuloma annulare
Hypopigmented and somewhat atrophic skin behind a row of advancing papules (has been mistaken for vitiligo by experienced clinicians)
Histologic Findings
Unusually large numbers of elastic fibers occur in the papillary dermis. Both light and electron microscopy examinations show that the elastic fibers have an abnormal appearance. Elastic fibers are swollen and clumped in the idiopathic and reactive forms of the disease and have a thorny appearance in penicillamine-induced EPS, resembling bramble bushes or barbed wire. Abnormal elastic fibers, along with collagen fibers, inflammatory cells, and other cellular debris, comprise clumps of material that are extruded via an inflammatory granulomatous reaction. Two studies from Japan have reported the presence of a 67-kd receptor for elastin in the epidermis of EPS lesions. These may assist in the transport of the fibers to the surface. Acid orcein-Giemsa stain highlights the components of the clumps, and aldehyde fuchsin stain demonstrates elastic fibers as a major constituent of the clumps. Verhoeff-van Gieson stain also may be used to highlight elastic fibers. As these masses impinge upon the epidermal base, an opening is created, and the material passes through it. Elastic fibers turn bright red with hematoxylin and eosin stain (see Media File 4). The clump's arrival at the surface signals the development of epidermal papular umbilication and the eventual disgorgement of its contents to the exterior.
Medical Care
Little medical treatment is required, except to monitor for internal vascular complications.
- Although many medications have been tried, no uniformly effective medications have been reported.
- A few reports suggest benefit from isotretinoin, but little confirmation is available.
- If pruritus is present, symptomatic therapy with camphor-containing and/or menthol-containing products is beneficial.
- A 2002 report described effective treatment with topical tazarotene in 2 patients.
- A 2006 case study described imiquimod as an effective treatment after 10 weeks of therapy.
Surgical Care
- Destructive methods appear to do more harm than good, often resulting in scarring worse than that expected from spontaneous healing.
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- Freezing with liquid nitrogen may have helped several patients.
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- Treatment with some laser techniques may have been modestly helpful in one patient with idiopathic EPS.
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- Treatment with flashlight pulsed dye laser has appeared to be beneficial in one reported case of EPS in a patient with Down syndrome.
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Activity
Avoid skin irritants.
A 2002 report described effective treatment with topical tazarotene in 2 patients, and a 2006 case study described imiquimod as an effective treatment after 10 weeks of therapy.
Drug Category: Retinoids
| Drug Name | Tazarotene (Tazorac) |
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| Description | Retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; may also have anti-inflammatory and immunomodulatory properties. |
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| Adult Dose | Apply thin film qd to cover lesion (2 mg/cm2); not to exceed >20% of BSA |
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| Pediatric Dose | <12 years: Not established
>12 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | X - Contraindicated in pregnancy
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| Precautions | May cause burning or stinging sensations; discontinue if excessive irritation; rinse thoroughly if contact with eyes, eyelids, or mouth; may cause severe irritation in eczematous skin; photosensitivity may occur |
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Drug Category: Immune Modulators
| Drug Name | Imiquimod (Aldara) |
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| Description | An immune system modulator that stimulates the TH1 response. Up-regulates INF-alpha, INF-gamma, and IL-12. Currently FDA approved for treatment of genital warts, actinic keratoses, and superficial basal cell carcinomas. One case study in 2006 described it as an effective treatment after 10 weeks of therapy. |
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| Adult Dose | Apply thin layer to affected area qhs for first 6 wk, then qod for 4 wk; rinse off in morning |
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| Pediatric Dose | <12 years: Not established
>12 years: Apply as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | C - Safety for use during pregnancy has not been established
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| Precautions | Most common adverse effects are erythema, skin irritation, skin peeling, skin edema, and, rarely, flulike syndrome |
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Further Inpatient Care
- No further inpatient care is expected unless internal complications require a systemic workup and/or intervention for complications.
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Further Outpatient Care
- EPS typically resolves without complications after a few years.
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Complications
- Vascular or visceral rupture is possible with systemic EPS.
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Medical/Legal Pitfalls
- Failure to educate EPS patients about the small risk of visceral involvement, although diagnosis by biopsy is not indicated, since false-negative findings are possible and no treatment options exist
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- Failure to heed the connection between EPS and the use of D-penicillamine
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We gratefully acknowledge the contributions of Willard Steck, MD, FACP, author of the previous edition of this article.
| Media file 1:
Elastosis perforans serpiginosa in an arciform pattern on nape of neck. |
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Media type: Photo
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| Media file 2:
Advancing serpiginous arrangement of elastosis perforans serpiginosa papules with mild scarring in their wake. |
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Media type: Photo
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| Media file 3:
Histologic section of elastosis perforans serpiginosa stained with hematoxylin and eosin. Connective tissue fibers and cellular debris are extruded through the epidermis via a spiraling path. |
 | View Full Size Image | |
Media type: Photo
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| Media file 4:
Cross-section of a nidus of fibers and debris of elastosis perforans serpiginosa in transit through the epidermis, stained with hematoxylin and eosin. Elastic fibers are red. |
 | View Full Size Image | |
Media type: Photo
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| Media file 5:
Connective tissue and debris of elastosis perforans serpiginosa emerging through the epidermis toward the surface, and elastic fibers in the nearby papillary dermis. The stain is a variation on acid orcein-Giemsa. Elastic fibers are black. |
 | View Full Size Image | |
Media type: Photo
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Elastosis Perforans Serpiginosum excerpt Article Last Updated: Jun 29, 2007
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