Am J Clin Dermatol 2007; 8 (6): 347-356

REVIEW ARTICLE 1175-0561/07/0006-0347/$44.95/0

© 2007 Adis Data Information BV. All rights reserved.

Palmar Erythema
Rocco Serrao,1 Matthew Zirwas2 and Joseph C. English III1
1 Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
2 Division of Dermatology, The Ohio State University Medical Center, Columbus, Ohio, USA

Contents

Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
1. Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
1.1 Primary Palmar Erythema (PE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
1.2 Secondary PE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
1.2.1 Hepatic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
1.2.2 Autoimmune . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
1.2.3 Endocrine/Nutritional . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
1.2.4 Infectious Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
1.2.5 Neoplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
1.2.6 Drug Induced . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
1.2.7 Primary Cutaneous Disease Manifesting as PE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
1.2.8 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
2. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354

Abstract Palmar erythema (PE), an often overlooked physical finding, is due to several physiologic or systemic
pathologic states. PE can exist as a primary physiologic finding or as a secondary marker of systemic pathology.
Primary or physiologic PE can be due to heredity, occurs in at least 30% of pregnant women as a result of
associated alterations in the function of the skin and its microvasculature, or may be a diagnosis of exclusion (i.e.
idiopathic PE).
Secondary PE from systemic pathology encompasses a wide range of disease states. Twenty-three percent of
patients with liver cirrhosis, from varying causes, can manifest PE as a result of abnormal serum estradiol levels.
Patients with a rare neonatal liver disease such as Wilson disease and hereditary hemochromatosis may exhibit
PE along with the other systemic manifestations of the genodermatoses. PE has been reported to occur in >60%
of patients with rheumatoid arthritis and is associated with a favorable prognosis. Up to 18% of patients with
thyrotoxicosis and 4.1% of patients with diabetes mellitus can have PE. This cutaneous manifestation of diabetes
occurs more often than the more classic diseases such as necrobiosis lipoidica diabeticorum (0.6%). PE can be
seen in early gestational syphilis and among patients with human T-lymphotrophic virus-1-associated
myelopathy. Drug-induced PE with hepatic damage has been documented with use of amiodarone, gemfibrozil,
and cholestyramine, while topiramate and albuterol (salbutamol) have been reported to cause PE in the setting of
normal liver function. Fifteen percent of patients with both metastatic and primary brain neoplasms may have
PE. Increased levels of angiogenic factors and estrogens from solid tumors have been postulated as the cause of
PE in such cases. Erythema ab igne can mimic PE, and patients with atopic diathesis are more likely to have PE
than matched control subjects. Smoking and chronic mercury poisoning are environmental causes of PE.
348 Serrao et al.

No treatment of primary PE is indicated. If medication is the cause of PE, the drug responsible should be
discontinued if possible. Identification of PE related to underlying disorders should be followed by treatment of
the underlying condition.
In light of the numerous etiologies of PE, this article reviews the current literature and provides a framework
to help guide the clinician in determining the cause of PE in patients presenting with this finding.

Palmar erythema (PE) is a well known physical finding most

commonly consisting of a symmetric, non-painful, non-pruritic,
slightly warm, non-scaling erythema most frequently involving
the thenar and hypothenar eminences of the palmar surface (figure
1).[1,2] On occasion, the palmar aspects of the phalanges and the
dorsal surface of the proximal nail folds may also be involved
(figure 2).[1,2] PE can exist as a primary physiologic finding or as a
secondary marker of systemic pathology in both adults and chil-
dren. This broad differential diagnosis can make the evaluation of
PE extremely challenging even to the experienced clinician (table
I and table II). PE should be carefully differentiated from normal
diffuse physiologic palmar mottling (figure 3), which involves the
entire palmar surface with specking of pale areas of 1mm or more
in diameter. This pattern varies with emotional states, elevation or
dependency of the hand, atmospheric temperature, and pressure on
the palm.[3]
A note on PE was published in 1942[1] and was followed by a
comprehensive review of causative factors of PE published in
1943.[2] We have endeavored to update the literature and to pro-
vide clinicians with guidance regarding the evaluation and treat-
ment of patients presenting with PE.

Fig. 2. Palmar, distal phalangeal and proximal nail fold erythema in a

patient with hepatitis C virus infection.

1. Etiology

While localization of erythema to the palms of the hands may

Fig. 1. Palmar erythema in a patient with connective tissue disease.
be due to the fact that this region has a higher density of arteriove-
nous shunts, the exact cause of PE varies with each disease state.[2]
Microscopic evaluation of patients with PE demonstrates in-
creased dilatation of capillaries and superficial arterial and venous
plexi in the palm compared with patients without PE.[4] The degree

© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (6)
Palmar Erythema
Table I. Conditions associated with palmar erythema in the adult[1-82]
Primary or physiologic
Hereditary; pregnancy; senile; idiopathic
Pathologic or secondary
Hepatic
Alcoholic cirrhosis; Wilson disease; hemochromatosis; hepatitis B virus
infection; hepatitis C virus infection; hepatopulmonary syndrome; portal
hypertension
Endocrine/nutritional
Thyrotoxicosis; diabetes mellitus; protein nutritional deficiency
Autoimmune
Rheumatoid arthritis; primary Sjögren syndrome; sarcoidosis; lupus
erythematosus; graft vs host disease
Infection
Brucellosis; trichinellosis; human T-lymphotrophic virus-1-associated
myelopathy; subacute bacterial endocarditis
Neoplasm
Metastatic and primary brain cancer; angiomyolipoma; leukemia; gastric
adenocarcinoma; Hodgkin lymphoma; lymphoproliferative disorders
Drug-induced reactions
Secondary to liver impairment (amiodarone, lipid-lowering agents)
Not associated with liver impairment (β2-sympathomimetic agents,
topiramate)
Cutaneous
Erythema ab igne; atopic dermatitis; red lunulae; livedo reticularis
Miscellaneous
Acrodynia; thallium poisoning; anti-thrombin III deficiency; chronic
obstructive pulmonary disease; smoking; ischemic heart disease; peptic
ulcer disease; arteriovenous fistula
of PE has been known to vary directly with the severity of a
specific disease, strongly suggesting that circulating factors are
etiologic.[2,5] Several studies have shown that there are increased
free estrogen levels in individuals with several of the conditions
known to cause PE, including hepatobiliary disease,[5,6] thyrotoxi-
cosis,[7,8] rheumatoid arthritis (RA), [3] and pregnancy.[9] Estrogens
are also known to have a proliferative effect on endometrial
capillary density and it is therefore likely that they play an impor-
tant role in the development of PE.[10]
Other suggested causative factors of PE include disordered
hepatic metabolism of bradykinin and other vasoactive sub-
stances.[11] In alcoholic liver disease there seems to be an indepen-
dent effect of alcohol leading to PE, but the overall effect of
alcohol seems to be directly related to the degree of liver impair-
ment.[12,13] Increased levels of angiogenic factors in solid tumor
neoplasms have been postulated as the underlying cause of PE
associated with cancer.[14]
© 2007 Adis Data Information BV. All rights reserved.
349
1.1 Primary Palmar Erythema (PE)
Primary or physiologic PE consists of hereditary PE or erythe-
ma palmare hereditarium (EPH), physiologic PE of pregnancy,
senile PE, and idiopathic PE (table I). EPH was first noted in
Europeans residing in the Gold Coast of West Africa as an area of
persistent, symmetric erythema of the palms and was extremely
common among Europeans in this area.[15] The color of the erythe-
ma was noted to vary from a slight blush to vivid scarlet and the
erythema was not confined to the distribution of a specific nerve.
No symptoms of systemic disease in patients with EPH were
described.[15,16] In 1929, Lane[17] documented two cases of EPH in
which both individuals recalled having family members with the
same physical findings and no concomitant systemic associations.
In one family, EPH has been documented over five generations,
with transmission consistent with an autosomal-recessive mode of
inheritance.[18]
In 1939, Feldman[19] noted a hyperemic “eruption of both
thenar and hypothenar eminences from the wrist to the base of the
fourth and fifth fingers” and areas that were “studded with vermil-
ion-colored spots, which [were] not elevated above the surface of
the skin” in a 32-year-old pregnant housewife. Since Feldman’s
first formal documentation of PE in pregnancy, it has been esti-
mated that approximately two-thirds of Caucasian women and
one-third of African American women will develop this vascular-
related change during pregnancy.[9] In a French study of 60 preg-
nant women, 18 (30%) had findings consistent with PE.[20] PE
usually manifests during the first trimester and is frequently ac-
companied by burning sensations, but ultimately undergoes re-
gression within 3 weeks’ postpartum.[9,21] Pregnancy is also asso-
ciated with alterations in the structure and function of the skin and
microvasculature, leading to the belief that a hormonal etiology,
most likely increased circulating estrogens, is responsible for the
Table II. Most common causes of palmar erythema in the child
Physiologic
Hereditary
Poisoning/ingestion
Acrodynia
Autoimmune
Kawasaki disease
Infectious
Congenital syphilis
Hepatic
Wilson disease
Hepatopulmonary hypertension
Am J Clin Dermatol 2007; 8 (6)
350
Fig. 3. Normal diffuse physiologic palmar mottling.
physiologic PE of pregnancy.[22] Several other physiologic vascu-
lar changes can also be seen during pregnancy[21] (table III). One
could consider this secondary PE but pregnancy is a physiologic
state and not considered a disease process.
There are, however, cases of PE during pregnancy that are
related to liver disease in pregnancy, and these cases should be
considered as secondary PE. Accompanying signs and symptoms
that are suggestive of liver disease during pregnancy are pruritus,
jaundice, epigastric or right upper quadrant pain, nausea or vomit-
ing, fever, pitting edema, and thrombocytopenia with or without
disseminated intravascular coagulation.[23] For example, PE that
manifests after 25 weeks’ gestation can be an indication of choles-
tasis of pregnancy. Cholestasis of pregnancy is characterized by
extreme generalized pruritus and jaundice with physical findings
consistent with abnormally elevated transaminase, alkaline phos-
phatase, bilirubin, and bile acid levels.[24] It has also been suggest-
ed that PE during pregnancy should be differentiated from all other
pathologic etiologies, including systemic lupus erythematosus and
thyroid disease, when other systemic signs suggestive of disease
are present, when the PE presents after the first trimester of
pregnancy, or when other cutaneous and/or systemic manifesta-
tions are present.[25]
Idiopathic PE is a diagnosis of exclusion after all feasible
physiologic and pathologic processes have been exhausted. In the
elderly, idiopathic PE has been found to develop without any
systemic associations, in which case it is primary PE.[26]
© 2007 Adis Data Information BV. All rights reserved.
Serrao et al.
1.2 Secondary PE
In 1932, Ambler[16] noted EPH in an Austrian Jewish man who
presented with PE and leukonychia. His “general health was
excellent with occasional attacks of abdominal pain” secondary to
chronic cholecystitis that occurred several years after the onset of
PE. At first this was thought to be similar to the findings of Lane[17]
in 1929; however, there was no evidence of PE in the patient’s
family history. This prompted the investigation of PE as a mani-
festation of systemic disease.
Secondary or pathologic PE has been reported to occur in
patients with hepatic, autoimmune, infectious, neoplastic, and
cutaneous diseases. Medication-induced PE differs from drug-
induced acral erythema of chemotherapy (i.e. palmoplantar ery-
throdysesthesia) in that PE is not painful. Since palmoplantar
erythrodysesthesia has been extensively reviewed elsewhere in the
literature[83,84] it will not be discussed further in this article. Acral
erythema from erythromelalgia is also excluded because it is
associated with significant symptoms and does not meet our
definition of the physical findings of PE.
1.2.1 Hepatic
In 1942, Perera[1] noted that cirrhosis of the liver was the most
frequent pathologic disease associated with PE. It was hypothe-
sized that increased vascularity due to increased levels of circulat-
ing estrogens was the primary cause of PE found in cirrhosis. This
conclusion was based on findings proving that estrogens are
inactivated by the liver.[6] Confirmatory evidence of estrogens
being a cause of PE was found when Bean[5] injected diethylstil-
bestrol and α-estradiol dipropionate into individuals with liver
disease and elderly White men without liver disease. PE subse-
quently developed in patients with impaired liver function but not
in control group.
In a study of 50 patients with non-alcoholic liver cirrhosis,
hepatic decompensation was associated with increased serum es-
tradiol, free estradiol, estradiol/testosterone, and free estradiol/
testosterone levels; an increased free estradiol/free testosterone
Table III. Common physiologic vascular changes associated with preg-
nancy[21]
Spider telangiectases
Palmar erythema
Non-pitting edema
Vasomotor instability
Gingival hyperemia
Hemorrhoids
Unilateral nevoid telangiectasia
Am J Clin Dermatol 2007; 8 (6)
Palmar Erythema 351

Table IV. Clinical signs of cirrhosis[31] presenting with PE in whom subsequent studies revealed cirrhosis
Sign Percentage of patients (n = 170) and portal hypertension.
Pedal edema 92 Alcohol is the most widely self-prescribed drug in the world
Ascites 89 and skin disease has been detected in over 40% of patients with
Jaundice 64 chronic alcoholism.[12] The cutaneous lesions of vascular spiders,
Clubbing 25 PE, and Dupuytren contracture have been found to have a com-
Palmar erythema 23 bined incidence of 72% in alcoholic cirrhosis.[38] Patients with
Terry nails 21 chronic alcoholism may exhibit increased flushing of the extremi-
Encephalopathy 19 ties and face.[39] This observation has led researchers to inquire
Testicular atrophy 4 about the possibility of an additional etiologic factor contributing
Gynecomastia 4 to PE in these patients. Possible candidates are a potent vasodilator
Pectoral area hair loss 2.4 neuropeptide known as calcitonin gene-related peptide and acetal-
Leukonychia 2.4 dehyde, the latter being a metabolite of ethanol.[12] In addition, the
Parotidomegaly 2 phytoestrogen content of alcohol has been thought to contribute to
Spider nevi 2 hypogonadal manifestations of alcohol abuse in men, including
Dupuytren contracture 0 PE.[40]
Caput medusae 0
Neonates and young children with underlying liver disease are
less likely to present with PE and other signs of chronic liver
level was observed in patients with PE, gynecomastia, and vascu- disease than adolescents and adults.[41] However, when PE is
lar spiders.[27] present in the newborn or young child, a pathologic cause must be
In addition to endocrine factors, numerous other biophysiologic considered. The etiology of the disease may be metabolic, infec-
changes have been investigated in patients with cirrhosis and PE. tious, developmental, and/or autoimmune. In addition, the patho-
In a study of 34 patients with liver cirrhosis and 24 control genesis of these diseases varies greatly depending on the age of the
subjects, local deterioration of peripheral cutaneous vasoconstric- child.[36] For example, Wilson disease is a relatively common
tor venoarterial reflexes was found on the palm but not on the inherited liver disease presenting with the stigmata of chronic liver
dorsum of the hand, leading to increased blood perfusion and disease in the school-aged child; hereditary hemochromatosis can
lower vascular resistance on the palms of patients with cirrho- present with abnormal liver function in the teenager; and α1-anti-
sis.[28] Another study of 14 patients with cirrhosis investigated the trypsin deficiency, cholesterol ester storage disease, and tyrosine-
effect of cirrhosis on capillary blood flow to the forearm but found mia can all present for the first time with signs and symptoms of
this to be no different than that in nine control subjects.[29] In a cirrhosis in late childhood/early adolescence.[42] Disorders of im-
study of 42 patients with compensated cirrhosis and 31 control paired liver function are often accompanied by the clinical picture
of hepatomegaly, splenomegaly, fever, hepatic bruit, vomiting/
subjects, increased blood flow, increased deep-body temperature,
diarrhea, developmental delay, distinctive odors, neurologic dete-
and reduced vascular resistance were found in the forearms of
rioration, purpura, eye findings, and dysmorphic features.[41]
patients with cirrhosis compared with the calves of patients with
cirrhosis.[30] This difference was not seen in the control subjects. 1.2.2 Autoimmune
In a study of 170 individuals with ultrasound-proven cirrhosis, RA is the most common disorder of connective tissues and
PE was demonstrated in as many as 23% of patients (table IV).[31] affects up to 1–3% of individuals in the Western world with a
PE has been frequently documented in diseases associated with female-to-male prevalence of 3 : 1.[43] PE is frequently encoun-
liver cirrhosis including alcoholic liver disease, Wilson disease, tered in RA but its presence in this context does not imply
hemochromatosis, hepatitis B virus infection, and hepatitis C virus underlying liver disease.[44] A study by Bland et al.[3] in 1958
infection.[32-36] For example, one study of 100 individuals with showed the incidence of PE to be >60% in patients with RA.
hepatitis C infection documented PE to be present in 24% of Interestingly, it appears that PE in RA constitutes a favorable
patients.[34] PE has also been associated with the hepatopulmonary prognostic sign in that patients with PE have a tendency to have
syndrome.[35] In addition, Kazumoto et al.[37] noted a 60-year-old fewer digital deformities and higher hemoglobin levels than indi-
woman with asymptomatic primary pulmonary hypertension viduals without PE. The pathogenesis of PE in RA remains un-

© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (6)
352 Serrao et al.

known.[45] PE has also been noted in 1–4% of patients with 1.2.3 Endocrine/Nutritional

systemic lupus erythematosus (SLE) along with the more common
skin changes of SLE, including non-cicatricial diffuse alopecia,
malar rash, photosensitivity, mucosal lesions, and pigmentary
changes.[46,47] In a study of 300 patients with primary Sjögren
syndrome, six patients had clinical signs of liver dysfunction,
including two patients with PE.[48]
PE is a documented cutaneous finding in post-bone marrow
transplant acute graft versus host disease (GVHD), typically mani-
festing between day 7 and day 21.[49,50] Cutaneous findings asso-
ciated with GVHD need to be distinguished from those due to high
doses of radiation and chemotherapy in the preparatory pre-trans-
plant regimen.[49]
Kawasaki disease or mucocutaneous lymph node syndrome is
an acute systemic inflammatory disease that has a predilection for
children aged <2 years, with most cases occurring before age 5
years.[51] The etiology of the disease remains unknown. Kawasaki
disease is a vasculitis that affects medium-sized vessels and the
coronary arteries in particular. Diagnosis is based upon recogni-
tion of a symptom pattern that includes fever for 5 days or longer
and at least four of the following: (i) non-exudative conjunctival
injection; (ii) oral involvement; (iii) changes in peripheral extremi-
ties, including PE; (iv) acute cervical adenopathy >1.5cm in
diameter; and (v) polymorphous rash. Erythema of the palms and
soles accompanied by a firm edema usually appears 3–5 days after
the first manifestations of the disease.[52] In a study of 39 US cases
of Kawasaki disease, PE and plantar erythema were present 90%
of the time.[53] However, Kawasaki disease does not always follow
a typical pattern of presentation. For example, one case study
documented a 6-year-old girl with a 2-day history of fever and
increasing anterior neck pain, torticollis, and odynophagia with
bilateral firm enlargement of cervical lymph nodes. Initial presen-
tation led to the presumption of a bacterial infection of the upper
aerodigestive tract as the cause. Eventually the girl developed PE
on day 3, non-purulent conjunctivitis on day 4, and strawberry
tongue on day 6; a subsequent diagnosis of Kawasaki disease was
made.[54]
Sarcoidosis is a multi-system granulomatous disease in which
cutaneous manifestations have been observed in about 25% of
Thyrotoxicosis is an endocrine disorder with several cutaneous
manifestations including PE, which has been found in up to 18%
of patients with the disorder.[58] In one documented case, bilateral
gynecomastia with accompanying PE and fine tremor were the
only findings on physical examination consistent with hyperthy-
roidism in a 49-year-old man.[8,58] Increased levels of circulating
estradiol-17β have been found in individuals with thyrotoxicosis
and this is therefore a likely causative factor for the development
of PE.[7]
Diabetes mellitus is a common disease with a variety of skin
manifestations due to microvascular complications, impaired
wound healing, and other undetermined mechanisms.[59] PE is an
associated microvascular complication seen in both in type 1 and
type 2 diabetes.[2,59] A recent study has demonstrated that PE is
found in >4% of patients with either type 1 or type 2 diabetes
(table V).[59]
PE has also been documented in malnourished elderly patients,
in whom the finding subsequently resolved with correction of
nutritional protein deficiency.[26]
1.2.4 Infectious Agents
In his initial note, Perera[1] documented the finding of PE in
individuals with subacute bacterial endocarditis. Since that time,
PE has been a documented finding in several infectious diseases
including gestational syphilis, human T-lymphotrophic virus-1
(HTLV-1)-associated myelopathy, brucellosis, and trichinellosis.
PE can manifest as a systemic sign of gestational syphilis.[51]
Gestational syphilis can manifest in the newborn in two distinct
patterns, depending on the gestational age at the time of infection.
Children that are infected with Treponema pallidum within the
first 4 months develop PE that is often accompanied by bullae and
erythema of the soles, has a shiny appearance, and subsequently
Table V. Microvascular manifestations seen in patients with diabetes mel-
litus[59]
Dermopathy Percentage of patients
(n = 162)
Shin spots (diabetic dermopathy) 15.3
Sclerodactyly 10.6
Rubeosis faciei 7.1
Palmar erythema 4.1

individuals.[55] Cliff et al.[56] noted PE with palmar burning and Huntley papules 2.4

itching as the initial presenting factor in a 53-year-old Indian Ecchymoses 1.2

woman with sarcoidosis. A 58-year-old man presenting with PE Pigmented purpuric dermatosis 1.2

with palmar burning and itching and a 3-week duration of hoarse- Granuloma annulare 0.6
Necrobiosis lipoidica diabeticorum 0.6
ness was also found to have sarcoidosis.[57]

© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (6)
Palmar Erythema 353

Patient with PE 1.2.6 Drug Induced

PE may be observed as a result of hepatic damage related to use

History, physical, and/or of medications. Amiodarone is an anti-arrhythmic commonly used
Yes Secondary PE. Treat
laboratory findings suggest
systemic disease (see table
underlying systemic for control of atrial fibrillation. Abnormal liver function is often
disease
VI for suggested work-up) reported with its use but symptomatic disease is rare.[67] However,
No in an elderly individual, use of amiodarone was found to result in
Family history of PE and/or Yes clinical signs of chronic liver disease, including PE.[67] Lipid-
EPH
childhood onset? lowering medications of the HMG-CoA reductase inhibitor (sta-
No tin) and fibric acid derivative classes have been associated with
Pregnant female?
Yes
PE of pregnancy drug-induced hepatitis.[68] Punthakee et al.[68] reported on a
No
63-year-old woman taking gemfibrozil and cholestyramime who
Yes presented with mild PE and a large firm liver as physical findings
Older adult? Senile PE
indicative of liver dysfunction.
No
Other medications may cause PE directly without causing liver
Idiopathic PE dysfunction. Topiramate used for off-label treatment of paranoid
Fig. 4. Flow chart: evaluation of palmar erythema (PE). EPH = erythema schizophrenia has been reported to cause PE.[69] Infusion of al-
palmare hereditarium. buterol (salbutamol) in pregnant women for the prevention of
premature labor has been associated with development of both
results in desquamation several days after birth.[51] The eruption patchy PE and plantar erythema.[70,71] In an unusual case of PE of
may also be present in the perianal region, groin, axillae, and pregnancy, a patient was given albuterol at 17 weeks’ gestation to
around the neck. However, if infection occurred after the initial 4 reverse labor.[72] She subsequently developed PE 5 days after the
months of pregnancy the classic maculopapular rash of secondary infusion of albuterol began and the PE resolved on post-partum
syphilis will be present.
Table VI. Suggested work-up of a patient presenting with palmar erythema
PE, along with xerosis, dermatophytosis, seborrheic dermatitis,
and candidiasis, was found to be a significant finding in individu- Recommended in all patients
Complete history and physical examination
als with HTLV-1-associated myelopathy when compared with
Liver function tests
control patients.[60] Although PE from brucellosis and trichinel-
Blood urea nitrogen/creatinine
losis has been documented in only one individual for both dis-
Hepatitis C virus serology
eases, it is worthwhile to note that PE can be a manifestation of
Hepatitis B virus serology
varied infectious processes.[61,62]
Ferritin
Fasting glucose
1.2.5 Neoplasia
Thyroid-stimulating hormone
PE has been reported as a paraneoplastic finding. Noble et al.[14] Complete blood count
noted that PE was found in >15% of individuals with both meta- Chest x-ray
static and primary brain neoplasms. In addition, these investigators Consider ordering based on clinical suspicion
previously noted that PE was associated with metastatic cancers of Ceruloplasmin
both the cecum and the tongue.[14] PE was noted as a physical Proalbumin, albumin
finding in an individual with Hodgkin lymphoma and in an indi- Rheumatoid factor
vidual with gastric adenocarcinoma.[1,63,64] PE associated with Anti-nuclear antibody, SSA, SSB
lymphoproliferative disorders has also been reported in two sepa- Magnetic resonance imaging of the brain
rate studies, both documenting involvement in one individual.[1,65] CT scan of the chest, abdomen, pelvis
PE has also been associated with hepatic tumors, such as Bone marrow biopsy

hepatic angiomyolipoma.[66] It may be hypothesized that the etiol- Rapid plasma reagin, fluorescent treponemal antibody absorption assay

ogy of PE in hepatic angiomyolipoma is due to impaired liver Anti-human T-lymphotrophic virus-1 titer
SS = Sjögren syndrome.
function and thus increased levels of circulating estrogens.

© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (6)
354
day 3. It is postulated that β2 sympathomimetic agents may
aggravate the vascular effects of estrogens in pregnant women and
may also be present in glomus bodies of the palms and soles,
leading to the patchy appearance of the PE and plantar erythe-
ma.[70]
In a review of the cutaneous complications of hormone replace-
ment therapy, cutaneous findings including nevocellular nevi,
vascular spiders, chloasma, hyperkeratosis of the nipples, and
acanthosis nigricans – but not PE – were noted.[73] Neither predni-
sone nor oral contraceptives have been reported to cause PE.
1.2.7 Primary Cutaneous Disease Manifesting as PE
Erythema ab igne of the palms has been mistaken for PE. A
42-year-old baker was found to have hyperkeratotic lesions on
reticular erythema of his palms and volar digits.[74] Immunofluor-
escence studies revealed a lack of type IV collagen in the basement
membrane zone of the palmar surface. The finding may have been
due to digestion of collagen type IV by heat-activated matrix
metalloproteinases; work-related heat exposure may also cause
hyperproliferation of keratinocytes.
Atopic skin diathesis is a clinical term used to describe patients
with skin atopy and previous, present or future atopic eczema/
dermatitis syndrome (AEDS).[75] PE has been found to be a
statistically significant cutaneous finding in patients with AEDS
compared with control subjects, perhaps providing an additional
method for clinical assessment of atopic skin diathesis by
clinicians.[75,76]
Red lunulae have been found to be an associated cutaneous
finding with PE. In a study of five patients with red lunulae, two
had accompanying PE.[77] Both patients were elderly Caucasian
men with worsening chronic obstructive pulmonary disease. It was
speculated that the two conditions may be expressions of disease at
different sites of a common unknown vasodilatory process.
Livedo reticularis (LR) has also been found to be an associated
cutaneous finding with PE. One study found that PE and LR were
each present in 4% of patients with SLE.[47] LR also accompanied
PE and cyanosis of the extremities in a 34-year-old woman with a
familial deficiency of anti-thrombin III.[78] In addition, patients
with RA who develop rheumatoid vasculitis can have extra-articu-
lar manifestations of both PE and LR.[44] LR has also been demon-
strated in HTLV-1-associated myelopathy and in brucellosis, dis-
eases in which association with PE has been mentioned.[60,61]
1.2.8 Miscellaneous
Several diseases not easily categorized have been reported to
present with the physical finding of PE. Exposure to chronic
mercury poisoning (acrodynia) and thallium intoxication are two
© 2007 Adis Data Information BV. All rights reserved.
Serrao et al.
such entities.[79-81] McArthur and Firkin[65] demonstrated chronic
obstructive pulmonary disease, ischemic heart disease, and peptic
ulcer disease as other potential associations with PE and reported
that smoking is a possible independent factor leading to the
development of PE. PE has also been reported to have been
aggravated by an arteriovenous fistula in a patient with hepatitis B
virus infection.[82]
2. Treatment
In cases of primary PE, no treatment is indicated. When the
cause is secondary to medication use, possible discontinuation of
the drug or switching of the drug to a different class should be
advised when feasible. When underlying disorders are identified,
management needs to be directed at the treatment of these specific
disorders.
3. Conclusion
The variety of possible associated factors means that evaluation
of a patient presenting with PE can be a challenging task (table I).
It is very important for the patient to be evaluated carefully with a
comprehensive history and physical examination. The history of
illness should include specific inquiries about the nature of the
onset of PE, previous episodes of PE, and other systemic and/or
cutaneous symptoms/signs. A complete list of current medications
should also be elicited from the patient. If the patient is female,
pregnancy status should be determined. Other areas of interest
include a family history of PE, a history of liver disease, alcohol-
ism, rheumatic/autoimmune disease, endocrine abnormalities, nu-
tritional deficiency infection, neoplasm, and potential toxin expo-
sure. In addition, Kawasaki disease and gestational syphilis also
need to be considered in children. Certain physical findings with
laboratory examination results are suggestive of specific disease
processes (figure 4 and table VI). Palmar biopsy is not common
practice in the diagnosis and/or management of PE.
PE presents as a diagnostic challenge. We have reviewed the
recent literature and simplified the evaluation process in an al-
gorithm format (figure 4). Treatment is not indicated for primary
PE but should be directed at the underlying disorder, relevant drug,
or other cause when secondary PE is diagnosed.
Acknowledgments
No sources of funding were used to assist in the preparation of this review.
The authors have no conflicts of interest that are directly relevant to the
content of this review.
Am J Clin Dermatol 2007; 8 (6)
Palmar Erythema
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Correspondence: Dr Joseph C. English, III, Residency Program Director,
Department of Dermatology, University of Pittsburgh, 190 Lothrop Street,
Suite 145 Lothrop Hall, Pittsburgh, PA 15232, USA.
E-mail: englishjc@upmc.edu
Am J Clin Dermatol 2007; 8 (6)