Dress Syndrome

What is Dress Syndrome?

Dress is an abbreviation of ‘Drug reaction with eosinophilia and systemic symptoms’. This is an adverse reaction of drugs which potentially causes life-threatening, hypersensitivity reaction and involving systemic circulation and major organs including lungs, liver, and kidney. Dress syndrome is a rare condition.

The onset of Dress syndrome is not instant but usually takes two to eight weeks after exposure to the drug. Prolonged intake or exposure to the drug leads to relapsing the syndrome and often associated with the latent human herpesvirus infection reactivation. ^{[1, 5]}

Causes

Dress syndrome is delayed responsive reaction of T-cell. The following causes may associate with Dress Syndrome

• Genetic predisposition towards drug hypersensitivity syndrome
• Defective drug metabolism in the liver
• HHV6 (human herpes virus 6) re-activation ^[2,3]

Symptoms

The included symptoms for Dress syndrome include a broad range of clinical manifestations. All the clinical features may not be immediate reactions but gradually appears within two to eight weeks after exposure to the culprit drug. The associated symptoms can be divided into two categories:

• General symptoms
• Dress syndrome rash (Cutaneous manifestations)
• Visceral involvement ^[4,5]

General symptoms

The following are the general symptoms associated with the Dress Syndrome:

• Fever
• Rash
• Lymphadenopathy (LAP) at two sites
• Blood cell abnormality including leukocytosis and eosinophilia
• At least one internal organ involvement. In majority, liver affected mostly and resultant with this cause liver function test abnormality as similar as viral hepatitis

Visceral involvement

Dress is considered as serious drug adverse effect because it affects several internal organs and causes severe morbidity and related mortality. The included morbidities are hepatitis, colitis, nephritis, pericarditis, myocarditis and pneumonitis. Most common associations are leukocytosis with eosinophilia with or without mononucleosis.

Dress Syndrome rash

The following typical multiple cutaneous manifestations are common:

• Urticaria with maculopapular eruption
• Skin problems including skin vesicles, round large blister filled with fluid (bullae), small pimple-shaped blister filled with pus (pustules), inter-vascular bleeding cause purple colored spots on skin (purpura)
• Target lesion is another type of rounded three distinct concentric color zone with fluid accumulated skin lesion.
• Facial edema or face become fluffy due to fluid retention in the body
• Inflammation of the skin around the mouth and lips (cheilitis)
• Dermatitis exfoliativa or the entire skin become swelled, reddened with prominent scaling

Diagnosis

The usual diagnosis of dress syndrome is based upon clinical manifestations, including consideration of latency period and omission of alike non-drug-induced conditions.

The various kind of diagnostic criteria are established, but none of these are precise to diagnose Dress syndrome. Even different healthcare organization set their different standard procedure to diagnose DRESS syndrome, among this HHV-6 activation also included.

Re-challenging

Re-challenging is considered as gold standard for detecting the adverse event causing drugs. but in DRESS syndrome, clinically it is not acceptable to re-challenge with the suspected drug for detection, as the consequences are life threatening.

Lymphocyte transformation/activation test

This test is not provided standard result for most of the drugs due to its low sensitivity and specificity. Lymphocyte transformation/activation test may provide negative test result in the acute case of DRESS syndrome.

Patch testing in DRESS

This test result can able to detect drug-induced delayed hypersensitivity reaction for some cases, though the success rate is only 32.1%. The success of the result depends upon the used drug therapy, as this test can detect antiepileptic drugs like CBZ successfully with the minimum result for tenoxicam. But provide negative result in allopurinol-induced DRESS syndrome.

Genetic testing

The investigational study found genetic testing is a promising diagnosing tool for future. Investigators prefer before prescribing enlisted drugs, which can cause DRESS syndrome genetic test performance can reduce the risk of DRESS syndrome. Before prescribing suspected drugs, genotyping for HLA markers can be used as screening tools. [5,6]

Generally, following methods are performed to detect the DRESS syndrome.

• Skin Biopsy
• Hematological tests include Complete blood count (CBC), and clotting test
• Internal organ functioning tests can also order for major organ involvement including liver function test, muscle enzyme test, and kidney function test
• Serological test specifically for certain virus, including HHV-6, hepatitis B, C, CMV and EBV
• Endocrine functionality tests including serum glucose level, thyroid testing
• Urinalysis is carried out to evaluate renal involvement
• ECG, echocardiogram, and chest X-ray for assessing the heart and lung condition.
• CT scan of brain, liver, and kidney can require performing depending upon the patient condition.
• Scans may be performed to evaluate liver, kidney, and brain depending on symptoms and the results of initial tests. [7]

Treatment

The foremost therapeutic management for DRESS syndrome is to stop to take all suspected drugs. Then provision of supportive care according to patient need, including fever management, monitoring of vital signs, rash observation, and overall close monitoring.

Diagnostic tests like hematological analysis immediately require, depending upon the test result treatment approaches are applied.

Steroidal drugs

Steroidal injections usually prescribed to control hypersensitivity reaction. But once the condition is settled, stopping of steroid administration may cause recurrence of the symptoms. Therefore, gradually reduce the dose of steroidal injections with close monitoring of the patient.

Other systemic administered drugs

Immunoglobulins, immunomodulatory drugs and plasmapheresis category of drugs such as cyclophosphamide, rituximab, mycophenolate  etc are prescribed.

Supportive treatment

• Supportive care also requires treating skin lesions, such as dressing, topical application of steroidal drugs, antihistamines, and emollient.
• Electrolyte balancing, fluid administration, and proper calorie maintenance are also important for treating DRESS syndrome.
• Antibiotics can be prescribed in case of secondary infection
• Expert nursing care with proper hygiene, warm environment provide quick recovery. ^[1,2,7,8]

References

1. Jean-Claude Roujeau (2016); Drug reaction with eosinophilia and systemic symptoms (DRESS); http://www.uptodate.com/contents/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress
2. Zain Husain, Bobby Y. Reddy, Robert A. Schwartz; DRESS syndrome; http://www.jaad.org/article/S0190-9622(13)00154-0/fulltext
3. Marcia L. Buck (2016); DRESS Syndrome; Medscape; http://www.medscape.com/viewarticle/776164_3
4. Vittorio CC, Muglia JJ. Anticonvulsant hypersensitivity syndrome. Arch Intern Med. 1995;155:2285–2290
5. Sonal Choudhary, Michael McLeod, Daniele Torchia, Paolo Romanelli; Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome; J Clin Aesthet Dermatol. 2013 Jun; 6(6): 31–37
6. Kano Y, Hirahara K, Mitsuyama Y, et al. Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption. Allergy. 2007;62:1439–1444.
7. Marius Rademaker; Drug hypersensitivity syndrome;  DermNet NZ ; http://www.dermnetnz.org/topics/drug-hypersensitivity-syndrome/
8. Patrice Cacoub, Philippe Musette, Vincent Descamps, Olivier Meyer, Chris Speirs, Laetitia Finzi, Jean Claude Roujeau, The DRESS Syndrome; doi:10.1016/j.amjmed.2011.01.017; http://www.aahs.org/medstaff/wp-content/uploads/dresssyndromeajm2012.pdf