Generalised eruptive keratoacanthomas

What is a keratoacanthoma?

Keratoacanthoma is a common type of cutaneous squamous cell carcinoma. It is characterised by rapid evolution, and often, by self-healing over a few months.

What are generalised eruptive keratoacanthomas?

Generalised eruptive keratoacanthomas (Grzybowski syndrome) refers to a very rare disease in which hundreds of keratoacanthoma-like papules appear.

It should be distinguished from an inherited disorder, multiple self-healing squamous epitheliomas of Ferguson-Smith, in which multiple keratoacanthomas appear in children and young adults. Witten and Zak described a similar condition in which there were giant keratoacanthomas.

Who gets generalised eruptive keratoacanthomas?

Only about 30 cases of generalised eruptive keratoacanthomas have been written up in medical journals worldwide. The syndrome affects middle-aged adult males and females equally.  

What is the cause of generalised eruptive keratoacanthomas?

The cause is unknown. Because in some ways these lesions look and behave like viral warts, several investigators have looked for evidence for human papillomavirus within the lesions. The results have been inconclusive, but in most cases, no evidence of viral infection has been found.

What are the clinical features of generalised eruptive keratoacanthomas?

The patient with generalised eruptive keratoacanthomas presents with multiple itchy papules and nodules, which start abruptly and increase in number over some months. The main features are:

• Severe itch
• Numerous firm bumps on all affected areas (face, scalp, trunk and limbs)
• White bumps in the mouth (lips, tongue, inside the cheeks)
• Larger horny nodules that persist for a few weeks, then disappear by themselves
• Koebnerisation — the nodules may appear at sites of skin injury
• Mask-like facial appearance, due to thickened facial skin
• Ectropion (drooping lower eyelids) and retraction of eyelid skin
• Hoarseness due to nodules on the larynx.

Oral and perioral papules

Eyelid retraction

Diffuse eruption on chest

Eruptive keratoacanthomas

Eruptive keratoacanthomas

Diffuse rash

How do generalised eruptive keratoacanthomas compare with regular keratoacanthomas?

An individual papule or nodule seen in generalised eruptive keratoacanthomas resembles a keratoacanthoma.

• Both are characterised by a keratotic papule that grows quickly and may spontaneously resolve after a few weeks or months.
• Keratoacanthoma does not result in severe itch or cause tight facial skin or eyelid retraction. 
• A keratoacanthoma is derived from hair follicle cells and does not normally affect mucosal surfaces such as the mouth, a common location for generalised eruptive keratoacanthomas.
• Keratoacanthoma is most commonly found on sun-exposed areas; the lesions of generalised eruptive keratoacanthomas may arise on any site. 
• Progression to metastatic squamous cell carcinoma does not occur, and general health is unaffected.

How are generalised eruptive keratoacanthomas diagnosed?

The diagnosis is a clinical diagnosis supported by a skin biopsy that shows similar histological changes to keratoacanthoma or cutaneous squamous cell carcinoma.

Skin biopsy reveals:

• Keratin-filled core
• A thickened squamous layer of the skin
• Atypical skin cells (keratinocytes)
• A proliferation of keratinocytes extending into the dermis (lower layer of skin)
• Mild inflammation.

Most individuals with generalised eruptive keratoacanthomas are otherwise in good health, and blood test results are normal.

What is the treatment for generalised eruptive keratoacanthomas?

Treatment fails for many patients with generalised eruptive keratoacanthomas. Only one case has been reported to clear up spontaneously. In other cases, improvement or complete resolution has occurred with one of the following medications:

• Acitretin
• Isotretinoin
• 5-Fluorouracil
• Methotrexate
• Cyclophosphamide.

Symptoms can be eased with emollients and anti-itch medications.

Untreated, it is reported to persist indefinitely.