National Skin Centre, Singapore

Guidelines on Erythroderma/ Generalised Exfoliative Dermatitis

Definition

Erythroderma or generalized exfoliative dermatitis (GED) is defined as an

inflammatory skin disorder with erythema and scaling occurring in a
generalized distribution involving more than 90% of the body surface area.
The challenge for the clinician is to identify and treat the underlying disease.

Etiology

5 broad categories of underlying causes are:

1.) Preexisting dermatoses (53%)1:

I; Atopic dermatitis
II; Psoriasis
III; Pityriasis rubra pilaris
IV; Seborrhoeic dermatitis
V; Contact dermatitis, including airborne and
phytophotocontact dermatitis
VI; Chronic actinic dermatitis
VII; Ichthyoses (infants and young children)

2; Drug eruptions (5%)

e.g. antiepileptics, antihypertensives (captopril, frusemide),
antibiotics (penicillins, sulphonamides), allopurinol

3; Malignancy (16%)
I; CTCL (including Sezary syndrome) most common
II; Hodgkins disease 2nd most common
III; Non-Hodgkins lymphoma
IV; Leukemia, myelodysplasia
V; Visceral malignancies (rarely) e.g. prostate, thyroid, lung,
liver, ovarian, rectal, mammary

4; Miscellaneous disorders (rare)

I; Immunobullous disorders e.g. pemphigus foliaceus
II; Lichen planus
III; Crusted scabies
IV; Dermatophytosis, candidiasis
V; AIDS
VI; GVHD, including post-operative exfoliative dermatitis

5; Idiopathic (26%)

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History

It is important to ascertain the etiology of GED in order to manage it properly.

The general medical history may reveal a preexisting dermatosis such as
atopic dermatitis or psoriasis, or a family or personal history of atopy. The
patient may have had characteristic psoriatic plaques, flexural dermatitis or
immunobullous skin lesions for months or years prior to the development of
GED. A drug history and history of contact with chemicals or topical
medicaments is important. Aggravating factors, such as sunlight, should be
elicited. A systemic review, including loss of weight, night sweats & bowel
changes, should be undertaken to evaluate for malignancy.

History is also targeted at eliciting complications of GED, such as cardiac

failure leading to orthopnoea & pedal oedema, hypoproteinemia leading to
pedal oedema, hypothermia & hyperthermia resulting in chills.

Clinical Examination

The relative proportion of erythema & scaling do not contribute to the

delineation of the underlying disorder. Areas of involvement and percentage of
body surface area affected should be charted. Islands of sparing are typically
seen in pityriasis rubra pilaris, and deck-chair sign in papuloerythroderma of
Ofuji, but they are not specific for these conditions. Keratoderma of palms and
soles may be a sign of pityriasis rubra pilaris or chronic idiopathic
erythroderma: the latter may have a higher incidence of progression to CTCL.
Dystrophic nails and hair loss also seem to be associated with more severe
and chronic erythroderma.

Lymphadenopathy occurs in up to 71%: this may be due to dermatopathic

lymphadenopathy (80%) or secondary to lymphoma (20%). A thorough
general examination including chest examination, palpation of the abdomen,
per rectal examination, breast & pelvic examination (in female) should also be
undertaken.

Complications of erythroderma should be specifically looked for. Pitting

oedema of the legs may indicate high-output cardiac failure (if in association
with lung crepitations) or hypoproteinemia, but pedal oedema is more
commonly due to inflammation of the skin. Other complications to note are
hyper- or hypothermia, secondary impetinization, dehydration, pallor
(anemia), malnutrition (exacerbated by extensive scaling, oozing or
hypermetabolism).

Investigations

Routine laboratory evaluation in GED is generally not helpful in determining a

specific diagnosis, with the exception of histopathology in the diagnosis of
cutaneous lymphomas. Specific investigations may be useful where clinically
indicated, in evaluation for underlying maliganancy.

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A) The following basic screening investigations are recommended:

Full blood count and ESR: INFECTION?

Peripheral blood film
Buffy coat for Sezary cells> fsp ou 1000/mm3: LYMPHOME
Urea, creatinine & electrolytes; PERTES DEAU
Liver function test: HYPOALBUINEMIE
Chest X-ray
Skin biopsy for histology (at least 2 sites); DIF if immunobullous
disease suspected
Total IgE and LDH (senile erythroderma with serum hyperIgE)
Stool for occult blood x 3
Urinalysis
Tumour markers (not routinely done by other centres. Tumor markers are not deemed
suitable for screening for malignant disease; their principal applications are in monitoring of
therapy and prognosis. Ref: Harrisns Principles of Internal Medicine 13thEd)
PSA (prostate Ca)
Alpha-fetoprotein (hepatoma, testicular Ca, hepatitis)
CEA
- Malignancies: colorectal, thyroid medullary, non-
small cell lung, pancreas, stomach, breast;
- Benign conditions: smoking, chronic lung
disease, alcoholic cirrhosis, hepatitis,
inflammatory bowel disease
Ca 125 (ovarian Ca)
Ca 19-9 (pancreatic Ca)

B) Additional investigations may be needed where indicated:

Lymph node biopsy & CT (abdo, pelvis) if lymphadenopathy present

Abdominal ultrasound or CT abdomen if hepatomegaly
Myeloma panel if ESR markedly elevated or widened serum protein-
albumin gap
Staging investigations if CTCL on histopathology (refer to guidelines on
Management of Mycosis Fungoides)
Refer to appropriate specialist for evaluation for malignancy if initial
screening investigation abnormal

Management in acute phase

In the acute phase, treatment consists of:

A; Management of complications:
Systemic antibiotics for secondary infection:
- e.g. cloxacillin
Correction of fluid and electrolyte abnormalities:
- e.g oral rehydration if no electrolyte abnormalities

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 - rehydration with IV normal saline if hyponatremic
Correction of nutritional deficiencies
- e.g. Promod 1 scoop /day if hypoalbuminemic
- Ensure supplements if cachexic
Provision of appropriate ambient temperature:
- warm ambient temperature if having chills/ hypothermic
Cardiology consult and diuretics for high-output cardiac failure

B; Measures to soothe the inflamed skin. The following is recommended:

Emulsifying ung as soap

0.05% to 0.1% betamethasone valerate cream or ung bd to trunk/limbs;
0.025% betamethasone valerate cr to face/ flexures bd
Emollients e.g WSP or WSP:LP
Antihistamines e.g. hydroxyzine 25mg tds
Cessation of all unnecessary drugs; substitution of recently added
drugs with unrelated alternatives.

As the acute phase resolves, one may see more definitive features of an
underlying skin disorder, and treatment may be more focussed:

A. Management of Erythrodermic Psoriasis

First Line Treatment

Methotrexate (if no contraindications) starting at 7.5 -10mg /week;

FBC after 1 week then monthly;
recheck FBC 1-2 weeks after any dose escalation
LFT 3 monthly
Liver biopsy at cumulative dose of 1500mg

Second Line Treatment

Acitretin 25mg - 30mg om;

Baseline urine pregnancy test in females
Baseline fasting lipids & LFT, at 2 weeks then monthly x 4 mth,
then 3 monthly
Advise against pregnancy for 3 years after cessation
(esterification to etretinate by ethanol: longer half-life)

Third Line Treatment

Cyclosporin 3-5mg/kg/day
refer to guidelines on use of cyclosporin in atopic dermatitis

B. Management of Erythrodermic Atopic dermatitis & Erythrodermic

CTCL

Refer to respective NSC guidelines

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D. Management of idiopathic GED

First line: Topical corticosteroids and emollients

Second line: Prednisolone 0.5mg/kg/d in reducing doses
Third line: PUVA
Immunosuppressives e.g. azathioprine, CyA (for review
by senior consultant/ consultant first)

Prognosis and follow-up of idiopathic GED

87% complete or partial remission

13% persistent chronic GED higher risk for progression to CTCL.

Frequent surveillance for an underlying cause is advised.

Repeat biopsies from at least 2 sites every 6 months to 1 year in chronic
persistent GED, as a proportion may evolve over years into CTCL.

References

1; Sigurdsson V, Toonstra J, Hezemans-Boer M, Van Vloten WA. Erythroderma: a clinical

and follow-up study of 102 patients, with special emphasis on survival. J Am Acad
Dermatol 1996; 35:53-57.

2; Wilson DC, Jester JD, King LE. Erythroderma and exfoliative dermatitis. Clin Dermatol
1993; 11:67-72.

3. Sigurdsson V, Toonstra J, Van Vloten WA. Idiopathic erythroderma: a follow-up study of 28

patients. Dermatology 1997;194: 98-101.

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