DRESS SYNDROMEDrug reaction with eosinophilia and systemic symptoms By: Zainab Aleid

Group: (2)

30 April 2014

CASE VIGNETTE B

A 27 YO male, developed a red itchy skin rash. He has a seizures consequent to brain injury after trauma.Admitted to neurology department because inadequate controlling of seizures.

The patient treated with carbamazepine (now for 6months) and recently started with diazepam (for 4 days).Skin started itching about a week ago and become much worse during the last couple of days.

He feels ill, inspection of skin shows a maculopapular erythema over trunk and back.laboratory studies reveal elevated liver enzymes (AST 300, ALT 220,LDH650, gamma GT 150 ).

For last two days he had cough without sputum production and feel breathless.

LEARNING OBJECTIVES:

Differential diagnosis of the case. Diagnosis and Diagnostic tests. Management (Treatment, follow-up, prognosis) .

• Cutaneous drug reactions

• Viral or bacterial infections

• Hypereosinophilic syndrome

• Autoimmune connective tissue disease

May present with skin eruption, fever, and systemic symptoms

DIFFERENTIAL DIAGNOSIS

Type A reactions: are pharmacological effects that are predictable and dose-dependent and consist of side effects and drug interactions.

Type B reactions: are hypersensitivity reactions that are unpredictable and not dose-dependent, usually occurring at normally tolerated doses.

Hypersensitivity reactions frequently present as any type of skin rash and most common type is maculopapular erythema.

ADVERSE DRUG REACTIONS

DIFFERENTIAL DIAGNOSIS:There are many diseases develop rash because of drugs like :

oDrug reaction with eosinophilia and systemic symptoms (DRESS).

oStevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

oAcute generalized exanthematous pustulosis (AGEP).

Usually starts 4 to 28 days after drug exposure.

Severe mucosal involvement with erosions and bleeding on at least two sites.

Mild elevation of liver enzymes is frequent in SJS/TEN, but present in less than 10 percent of cases.

Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN

Acute generalized exanthematous pustulosis (AGEP)

Starts < 3 days after drug exposure. Characterized by hundreds or thousands pinpoint nonfollicular pustules disseminated over the body surface.

Internal organ involvement is rare.

Hypereosinophilic syndromes Marked peripheral eosinophilia.

Involvement of multiple organs such as the heart, GIT , lungs, brain, and kidneys.

manifestations include eczema, recurrent urticaria, and angioedema

Acute-onset systemic illness.

Generalized lymphadenopathy, hepatomegaly, splenomegaly, skin eruption, usually pruritic.

Systemic symptoms; Fevers, night sweats, Wt. loss.

ANGIO-IMMUNOBLASTIC T LYMPHOMA:

DRESS SYNDROME: (The most likely diagnosis)

Long latency period (2-8 weeks)

Drug-induced hypersensitivity syndrome (DIHS)

Also called ‘anticonvulsant hypersensitivity syndrome’, ‘drug reaction with eosinophilia and systemic symptoms’.

A serious adverse systemic reaction to a drug typically occurring 2–8 weeks after initial exposure.

CAUSES AND PATHOGENESIS:

Antiepileptics (particularly carbamazepine, phenobarbital and phenytoin) and allopurinol are the most common causes.

Others include:

Sulfonamides dapsone,

and vancomycin. (antibiotics).

The anti-gout drug.

viral reactivation

Association

between HLA and hypersensitivity

Deficiency of

detoxifying

enzymes

(HHV 6 and 7, CMV, EBV).

Inclusion criteria for potential cases require at least 3 of the following:

Hospitalization Reaction suspected to be drug related Acute skin rash Fever about 38 degrees Celsius Enlarged lymph nodes at two sites Involvement of at least one internal organ Blood count abnormalities such as low platelets,

raised eosinophils or abnormal lymphocyte count.

Diagnostic Tests

Confirmation of DRESS:• CBC with

differential and peripheral blood smear.

• Testing for HHV infection.

• Skin biopsy.

Exclusion of DDx:• Blood cultures• Antinuclear

antibodies• Serology for viral

hepatitis

Assessment of organ involvement:• Serum creatinine

and urinalysis.• Troponin and ECG.

Complete blood cell count with differential and peripheral blood smear – The finding of peripheral eosinophilia >700/microL suggests the diagnosis of DRESS. In some patients, lymphocytosis (absolute lymphocyte count >4500/microL) support the diagnosis of DRESS syndrome .

Serology for viral hepatitis –may be useful in excluding acute viral hepatitis in patients with abnormal liver function test results.

Serum creatinine and urinalysis – A moderate increase in creatinine level, low grade proteinuria, and abnormal urinary sediment with occasional eosinophils indicate kidney involvement.

• Liver function tests :

-Serum alanine aminotransferase (ALT) greater than twice the upper limit of normal values.

-And/or alkaline phosphatase greater than 1.5 times the upper limit of normal values on at least two different dates indicate liver involvement.

●Skin biopsy – The histologic findings of mild spongiosis and a lymphocytic infiltrate in the superficial dermis, predominantly perivascular, with eosinophils and dermal edema, although not specific, supports the diagnosis of a drug hypersensitivity reaction.

●Testing for herpesvirus infection – Active infection with human herpesvirus (testing for EBV, HHV-6, or HHV-7 is increasingly performed in patients with DRESS) , since viral infection reactivation may be a marker of prolonged course and increased risk of complications.

Patch testing

Essentially negative patch test reactions

 - reaction (hair dye discolouration)

 Irritant reaction

 +/- reaction

 + reaction

 ++ reaction

 +++ reaction

Imaging studies —

In patients presenting with nonspecific symptoms of pulmonary involvement (eg, cough, tachypnea/dyspnea),

Chest radiograph (CXR) or CT scan may provide evidence of interstitial pneumonitis and/or pleural effusion.

INTERSTITIAL PNEUMONITIS

PLEURAL EFFUSION

Management:

SUPPORTIVE THERAPY: Antipyretics; to reduce the effect of fever.

Topical steroids; to alleviate the skin manifestations.

Exfoliative dermatitis (erythroderma ): Warming of the environment . Correction of electrolyte disturbances. High caloric intake.

SYSTEMIC CORTICOSTEROIDS:

Internal organ involvement. Reduce symptoms of delayed hypersensitivity reactions. Inhibit the effect of IL-5 on eosinophil accumulation. Treatments prednisolone at a dose of 1 mg/kg/day Tapered gradually over a period of 6-8 weeks.

Monitoring —  Patients with DRESS should be monitored for progression of the skin eruption and/or development of clinical or laboratory symptoms related to organ involvement.

Laboratory tests are performed at weekly intervals in patients with favorable disease course.

Prognosis —

Most patients with DRESS recover completely in weeks to months after drug withdrawal.

summary What is the final diagnosis ?

Dress syndrome What is the cause?carbamazepine What further investigation the patient need?Skin biopsy , chest x-ray and CBC What is the treatment ? Drug withdrawl , Systemic steroid AND Supportive care

REFERENCES:

Kumar and Clark's Clinical Medicine, 8th Edition. Pages:1231.

http://emedicine.medscape.com/article/1049474-treatment

http://www.dermnetnz.org/reactions/sjs-ten.html

http://www.ijdvl.com/article.asp?issn=0378-6323;year=2011;volume=77;issue=1;spage=7;epage=15;..

http://www.uptodate.com/contents/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress