Life-threatening paraneoplastic cutaneous syndromes

doi:10.1016/j.clindermatol.2004.06.011

Clinics in Dermatology

Volume 23, Issue 3, May–June 2005, Pages 301-306

https://doi.org/10.1016/j.clindermatol.2004.06.011 Get rights and content

Abstract

Paraneoplastic syndromes are diseases or symptom complexes associated with malignancy, usually internal. In dermatology, we modify the definition to refer to dermatoses associated with internal malignancy. In this article, we discuss the link between malignancy and such dermatologic disorders as acanthosis nigricans, acrokeratosis paraneoplastica of Bazex, dermatomyositis, erythema gyratum repens, necrolytic migratory erythema (glucagonoma syndrome), and paraneoplastic pemphigus and discuss, where such information is known, the mechanism by which these paraneoplastic diseases occur.

Introduction

Paraneoplastic syndromes may be defined as diseases or symptom complexes that are associated with the presence of a malignancy. In dermatology we may modify this definition to refer to dermatoses that are associated with internal malignancy.¹ We have recently been reminded that, Helen O. Curth proposed the criteria to be satisfied to postulate an association between the malignancy and the cutaneous condition. These include:

•
concurrent onset and parallel course;
•
a characteristic type of associated malignancy;
•
a statistical association of the dermatosis and the malignancy;
•
a genetic link between the dermatosis and the malignancy.

Section snippets

Acanthosis nigricans

Arguably, the earliest recognized paraneoplastic syndrome is acanthosis nigricans (AN). Although this condition may be familial or can occur in association with obesity or endocrinopathy, and most recently has been regarded as a sign of insulin resistance,² extensive and severe AN is often associated with malignancy, particularly adenocarcinomas. Acanthosis nigricans is characterized by the presence of pigmented, velvety plaques most often seen on the sides and nape of the neck and other

Acrokeratosis paraneoplastica of Bazex

Bazex was first to establish an association between this uniquely distributed papulosquamous eruption and underlying malignancy.^a

Dermatomyositis

The characteristic heliotrope periorbital erythema and the poikilodermatous eruption characteristically occurring on extensor surfaces may occasionally be difficult to distinguish from cutaneous lupus. Dermatomyositis is described as presenting a violaceous erythema while lupus is generally more of a red color. Although the link between dermatomyositis and malignancy is controversial, reports of associations continue to appear in the literature. Interestingly, although childhood dermatomyositis

Erythema gyratum repens

Dermatologists are aware of several gyrate (gyrate from the Greek meaning a circle) erythemas, but one is virtually always indicative of internal malignancy. Erythema gyratum repens (repens from the Latin meaning to creep) was first reported in the literature and named by Gammel²⁴ in 1952. Since then, a number of patients have been reported and there appears to be a 2:1 ratio of men to women and the average age on onset is 63 years.²⁵ All reported patients with erythema gyratum repens have been

Necrolytic migratory erythema

This condition is almost unique among the paraneoplastic syndromes in that it is specific for a given tumor,⁴⁰ although there are reports of the rash occurring with other pancreatic diseases, malabsorption, and without any associated malignancy. It is typically associated with islet cell neoplasms, usually glucagonomas. The glucagonoma syndrome typically includes diabetes or glucose intolerance, and hyperglucagonemia, in addition to the rash. Other common manifestations include weight loss,

Paraneoplastic pemphigus

Among the most recently described paraneoplastic syndromes is paraneoplastic pemphigus (PNP). Historically, pemphigus vulgaris and pemphigus foliaceus have been reported in association with malignancy, but this association has been inconsistent (Table 1). Pemphigus has been associated with a variety of lymphoproliferative disorders, but this may be a function of the immunosuppressive drugs used to treat the blistering disease. Similarly, bullous pemphigoid was felt to be associated with

References (54)

J.E. Spellman et al.
Clonal interactions in a human squamous cell carcinoma
J. Surg. Res.
(1995)
P. Lingor et al.
Paraneoplastic polymyositis in recurring adrenal gland carcinoma
Lancet Neurol.
(2003)
H. Sekine et al.
Dermatomyositis associated with urachal adenocarcinoma
J. Urol.
(2002)
J.V. Joseph et al.
Dermatomyositis: a rare initial presentation of adenocarcinoma of the prostate
J. Urol.
(2002)
A.S. Boyd et al.
Erythema gyratum repens: a paraneoplastic eruption
J. Am. Acad. Dermatol.
(1992)
L.E. Eubanks et al.
Erythema gyratum repens
Am. J. Med. Sci.
(2001)
S.J. Garrett et al.
Erythema gyratum repens in a healthy woman
J. Am. Acad. Dermatol.
(1992)
S.E. Albers et al.
Erythema gyratum repens: direct immunofluorescence microscopic findings
J. Am. Acad. Dermatol.
(1993)
O.J. Stone
A mechanism of peripheral spread or localization of inflammatory reactions. Role of the localized ground substance adaptive phenomenon
Med. Hypotheses
(1989)
J.C. Langlois et al.
Erythema gyratum repens unassociated with internal malignancy
J. Am. Acad. Dermatol.
(1985)

P.R. Vandersteen et al.

Glucagonoma syndrome: a clinicopathologic, immunocytochemical and ultrastructural study

J. Am. Acad. Dermatol.

(1985)

C. Kiyokawa et al.

Envoplakin and periplakin are components of the paraneoplastic pemphigus antigen complex

J. Invest. Dermatol.

(1998)

A.L. Hovenden

Hypertrichosis lanuginosa acquisita associated with malignancy

Clin. Dermatol.

(1993)

R. Paul et al.

Itch and malignancy prognosis in generalized pruritus: a 6-year follow-up of 125 patients

J. Am. Acad. Dermatol.

(1987)

J. Callen

Dermatologic signs of systemic diseases

T. Hermanns-Le et al.

Juvenile acanthosis nigricans and insulin resistance

Pediatr. Dermatol.

(2002)

J.S. Flier

Metabolic importance of acanthosis nigricans

Arch. Dermatol.

(1985)

D.L. Ellis et al.

Melanoma, growth factors, acanthosis nigricans, the sign of Leser-Trélat, and multiple acrochordons: a possible role for alpha-transforming growth factor in cutaneous paraneoplastic syndromes

N. Engl. J. Med.

(1987)

A. Bazex et al.

Acrokeratosis paraneoplastica—a new cutaneous marker for malignancy

Br. J. Dermatol.

(1980)

J.L. Bolognia et al.

Bazex syndrome (acrokeratosis paraneoplastica) an analytic review

Medicine

(1991)

T. Tanaka et al.

A case of bullous pemphigoid and transitional cell carcinoma of the bladder

Arch. Dermatol.

(1983)

G. Soderdahl et al.

Differential expression of platelet-derived growth factor and transforming growth factor genes in small- and non-small–cell human lung carcinoma lines

Int. J. Cancer

(1988)

K. Iihara et al.

Growth-regulatory mechanism of two human esophageal-cancer cell lines in protein-free conditions

Int. J. Cancer

(1993)

J.M. Wishart

Bazex paraneoplastic acrokeratosis: a case report and response to Tigason

Br. J. Dermatol.

(1986)

D. Gill et al.

Bullous lesions in Bazex syndrome and successful treatment with oral psoralen phototherapy

Australas. J. Dermatol.

(2001)

S.E. Whitmore et al.

Dermatomyositis sine myositis: association with malignancy

Rheumatology

(1996)

J. Jorizzo

Dermatomyositis

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Life-threatening paraneoplastic cutaneous syndromes

Abstract

Introduction

Section snippets

Acanthosis nigricans

Acrokeratosis paraneoplastica of Bazex

Dermatomyositis

Erythema gyratum repens

Necrolytic migratory erythema

Paraneoplastic pemphigus

J. Surg. Res.

Lancet Neurol.

J. Urol.

J. Urol.

J. Am. Acad. Dermatol.

Am. J. Med. Sci.

J. Am. Acad. Dermatol.

J. Am. Acad. Dermatol.

Med. Hypotheses

J. Am. Acad. Dermatol.

J. Am. Acad. Dermatol.

J. Invest. Dermatol.

Clin. Dermatol.

J. Am. Acad. Dermatol.

Dermatologic signs of systemic diseases

Juvenile acanthosis nigricans and insulin resistance

Pediatr. Dermatol.

Metabolic importance of acanthosis nigricans

Arch. Dermatol.

Melanoma, growth factors, acanthosis nigricans, the sign of Leser-Trélat, and multiple acrochordons: a possible role for alpha-transforming growth factor in cutaneous paraneoplastic syndromes

N. Engl. J. Med.

Acrokeratosis paraneoplastica—a new cutaneous marker for malignancy

Br. J. Dermatol.

Bazex syndrome (acrokeratosis paraneoplastica) an analytic review

Medicine

A case of bullous pemphigoid and transitional cell carcinoma of the bladder

Arch. Dermatol.

Differential expression of platelet-derived growth factor and transforming growth factor genes in small- and non-small–cell human lung carcinoma lines

Int. J. Cancer

Growth-regulatory mechanism of two human esophageal-cancer cell lines in protein-free conditions

Int. J. Cancer

Bazex paraneoplastic acrokeratosis: a case report and response to Tigason

Br. J. Dermatol.

Bullous lesions in Bazex syndrome and successful treatment with oral psoralen phototherapy

Australas. J. Dermatol.

Dermatomyositis sine myositis: association with malignancy

Rheumatology

Dermatomyositis