Elastosis Perforans Serpiginosum 

Updated: Mar 06, 2019
Author: Elizabeth A Liotta, MD; Chief Editor: William D James, MD 

Overview

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). Elastosis perforans serpiginosa may be distinguished morphologically and histologically from other cutaneous diseases.

The first recognizable description of elastosis perforans serpiginosa was provided by Fischer in 1927 but was offered as an example of Kyrle disease. Jones and Smith also described elastosis perforans serpiginosa in 1947 but mistook it for porokeratosis of Mibelli. In 1953, Lutz recognized the features of elastosis perforans serpiginosa 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.

Elastosis perforans serpiginosa is a disease of connective tissue, possibly of autoantigenic etiology, that occurs in the following three forms:

  • Idiopathic elastosis perforans serpiginosa: The cause of idiopathic elastosis perforans serpiginosa is unknown; genetic predisposition is possible.

  • Reactive elastosis perforans serpiginosa: 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 elastosis perforans serpiginosa: This form is caused by the pharmacologic effect of D-penicillamine and occurs in approximately 1% of patients treated with the drug.

Pathophysiology

Elastosis perforans serpiginosa (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.

Etiology

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 elastosis perforans serpiginosa nor its spontaneous disappearance. Obviously, a secondary factor must be required to make elastic fibers provoke their own expulsion.

In reports and reviews of elastosis perforans serpiginosa, 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,[1] proper cross-linkage formation has been observed to occur with the assistance of lysyl oxidase, which is a copper-dependent enzyme.[2]  Penicillamine is a copper chelator and may interfere with the function of lysyl oxidase and the proper construction of elastic fibers.

Epidemiology

Frequency

Elastosis perforans serpiginosa is a rare condition. No geographic preferences are apparent for elastosis perforans serpiginosa.

Race

No racial differences have been reported for elastosis perforans serpiginosa.

Sex

Male-to-female ratio for elastosis perforans serpiginosa is approximately 4:1.

Age

Elastosis perforans serpiginosa usually appears during the second decade of life, but it may be seen in early childhood or late in life.

Duration

Elastosis perforans serpiginosa lasts a few years; however, in elastosis perforans serpiginosa cases associated with Down syndrome, elastosis perforans serpiginosa is a more prolonged and generalized eruption.

Prognosis

In most cases, cutaneous elastosis perforans serpiginosa 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.

 

Presentation

History

In elastosis perforans serpiginosa (EPS), 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.

Elastosis perforans serpiginosa usually is asymptomatic but can be pruritic. Secondary lesions are vague scars or areas of roughness and hypopigmentation or hyperpigmentation that result after the primary lesions have subsided and disappeared.

The three general categories of elastosis perforans serpiginosa are idiopathic, reactive, and drug induced.

Idiopathic elastosis perforans serpiginosa

Familial groupings have implicated both dominant and recessive types of inheritance. Inciting events are not known.[3, 4] Probably, 65% (or more) of elastosis perforans serpiginosa cases are idiopathic.

Reactive elastosis perforans serpiginosa

This form of elastosis perforans serpiginosa is 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 elastosis perforans serpiginosa. One reported case of elastosis perforans serpiginosa was seen in Moyamoya disease, which is a progressive occlusive disease of the cerebral vessels. This patient also had Down syndrome, so it is unclear if the elastosis perforans serpiginosa association was with Moyamoya disease and could be a marker of elastosis perforans serpiginosa.[5]

Perforating diseases that may occur in conjunction with elastosis perforans serpiginosa include reactive perforating collagenosis, perforating folliculitis, pseudoxanthoma elasticum,[6] and Kyrle disease.[7] Sufficient similarities and overlapping features are seen to suspect them of being variants of elastosis perforans serpiginosa in these patients; however, elastosis perforans serpiginosa is not associated regularly with diabetes, while the other three diseases usually are associated with diabetes. Reactive types comprise 25-30% of cases of elastosis perforans serpiginosa.

Drug-induced elastosis perforans serpiginosa

D-penicillamine appears to be the only drug for which elastosis perforans serpiginosa is an adverse effect. This form of elastosis perforans serpiginosa occurs in approximately 1% of treated patients. Usually, long-term treatment for Wilson disease provokes the occasional case of elastosis perforans serpiginosa, but its use in the treatment of cystinuria and rheumatoid arthritis has had similar effects. The elastosis perforans serpiginosa 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.

Physical Examination

Clinical features of elastosis perforans serpiginosa

Primary lesions are eruptive, dome-shaped, eventually umbilicated papules, measuring a few to several millimeters in diameter. Lesions are flesh colored to red. Usually, lesions are grouped in linear, arciform, circular, or serpiginous patterns, measuring several centimeters in diameter. New papules may appear in lines and figures that appear to migrate and enlarge peripherally.

Distribution of elastosis perforans serpiginosa

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. If multiple lesions are present, the figures may display a degree of anatomic symmetry.

Sites of elastosis perforans serpiginosa

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.[8] Another report from 2009 described a case induced by penicillamine therapy that occurred on the lip mucosa.[9, 10]

Elastosis perforans serpiginosa in an arciform pat Elastosis perforans serpiginosa in an arciform pattern on nape of neck.
Advancing serpiginous arrangement of elastosis per Advancing serpiginous arrangement of elastosis perforans serpiginosa papules with mild scarring in their wake.

Complications

Vascular or visceral rupture is possible with systemic elastosis perforans serpiginosa.

 

DDx

Diagnostic Considerations

Also consider the following:

  • 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)
  • Acquired perforating dermatosis
 

Workup

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 elastosis perforans serpiginosa and have a thorny appearance in penicillamine-induced elastosis perforans serpiginosa (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 elastosis perforans serpiginosa lesions. These may assist in the transport of the fibers to the surface.[11, 12]

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. The clump's arrival at the surface signals the development of epidermal papular umbilication and the eventual disgorgement of its contents to the exterior.

See the images below.

Histologic section of elastosis perforans serpigin 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.
Cross-section of a nidus of fibers and debris of e 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.
Connective tissue and debris of elastosis perforan 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.
 

Treatment

Medical Care

Little medical treatment is required for elastosis perforans serpiginosa (EPS), 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.[13]  A 2002 report described effective treatment with topical tazarotene 0.1% gel used daily at bedtime after 2 months of treatment in two patients. The lesions were noted to flare upon discontinuation of the therapy.[14] A 2006 case study described imiquimod as an effective treatment after 10 weeks of therapy.[15]

If pruritus is present, symptomatic therapy with camphor-containing and/or menthol-containing products is beneficial.

Photodynamic therapy with aminolevulinic acid reportedly was effective in a case of D-penicillamine–induced elastosis perforans serpiginosa.[16]

Cryotherapy has achieved improvement in some patients.[17, 18]

Surgical Care

Destructive methods appear to do more harm than good, often resulting in scarring worse than that expected from spontaneous healing.

Freezing with liquid nitrogen may have helped several patients.[19] Treatment with some laser techniques may have been modestly helpful in one patient with idiopathic elastosis perforans serpiginosa.[20] Treatment with flashlight pulsed-dye laser appeared to be beneficial in one reported case of elastosis perforans serpiginosa in a patient with Down syndrome.[21] More recently, a patient with elastosis perforans serpiginosa from prolonged therapy with D-penicillamine had complete regression of her lesions using fractional carbon dioxide laser for three sessions over a 6-month period, without resultant scarring.[22]

Activity

Avoid skin irritants.

Long-Term Monitoring

Elastosis perforans serpiginosa typically resolves without complications after a few years.

 

Medication

Medication Summary

A 2002 report described effective treatment with topical tazarotene in two patients,[14] and a 2006 case study described imiquimod as an effective treatment after 10 weeks of therapy.[15]

Retinoids

Tazarotene (Tazorac) cream or gel 0.05% or 0.1%

Tazarotene is a retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; it may also have anti-inflammatory and immunomodulatory properties.

Immune Modulators

Imiquimod (Aldara)

Imiquimod is an immune system modulator that stimulates the TH1 response. It up-regulates INF-alpha, INF-gamma, and IL-12. Currently, imiquimod is FDA approved for the 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.