- DRESS syndrome, also known as drug-induced hypersensitivity syndrome, is a severe cutaneous adverse reaction caused by certain medications. It is characterized by a rash, fever, lymphadenopathy, and involvement of internal organs like the liver, kidneys, lungs and heart. - The onset of symptoms occurs 2-6 weeks after starting the culprit drug. Affected individuals typically develop a widespread, often purpuric rash along with systemic inflammatory signs. The liver and blood counts are often impacted. - Diagnosis is based on clinical features and ruling out other conditions. Corticosteroids are the primary treatment but other immunosuppressants may be needed depending on severity. Identifying and stopping the

1. DRESS SYNDROME
- DR. VISALI P (PG)

2. • Also known as
• Drug induced hypersensitivity syndrome (DiHS)
• Hypersensitivity syndrome (HSS)
• Drug – induced delayed multiorgan hypersensitivity syndrome (DIDMOHS)

3. • Drug hypersensitivity reactions (DHR) are classified as immediate and non-
immediate.
• Immediate DHRs include urticaria, angioedema and anaphylaxis and occur
immediately or within the first 6 h after administration of the drug.
• Non-immediate DHRs tend to appear after many days of treatment, with a
delayed T-cell-dependent type of allergic mechanism and DRESS syndrome is
considered as one of them

4. History
• Presentation of Dress was initially noted with patients taking, phenytoin and termed
as Dilantin hypersensitivity.
• Patients presented with cutaneous adverse reaction, fever, lymphadenopathy and
systemic symptoms like hepatitis.
• Later was noticed with newer anticonvulsant like carbamazipine, and led to the term
‘Anticonvulsant hypersensitivity syndrome’
• Further severe adverse effects were noticed with Allopurinol and sulfones.
• Broadly termed as – DRESS by Bocquet et al.

5. Introduction
• Drug reaction with eosinophilia and systemic symptoms syndrome, one of the drug
induced Severe Cutaneous Adverse Reactions (SCARs)
• It is a life-threatening hypersensitivity disorder characterised by cutaneous lesions,
haematogical abnormalities and internal organ dysfunction.
• Mortality rate is about 10%

6. • Incidence : Varies between 1 in 1000 to 1 in 10,000
• Age group : Mean age of onset being 48 years
• Sex : Slight female preponderance
GENETIC FACTORS
Polymorphism in genes encoding HLA molecules
• Allopurinol - B*58:01
• Carbamazepine - A*31:01
• Phenytoin - B*13:01 and B*51:01
• Dapsone - B*13:01

7. Pathogenesis
1. Polymorphism in genes encoding the enzymes required for drug
metabolism, such as cytochrome P (CYP) 450 enzyme and N-
acetyltransferase.
- Decreased activity of metabolizing enzymes  accumulation of drugs or their
active metabolite  rendered antigenic when bound with a protein drug
specific immune response in patients with genetic background.
- This is known as Haptenization theory
- Among these polymorphisms, CYP2C9*3 showed the most significant
association

8. 2. p-i concept – pharmacological interaction of drugs with immune receptor
• Drug molecule will bind to the MHC via a protein bind to MHC or directly
through MHC groove.
• Presented by antigen-presentation cells, and are recognized as foreign antigens
• Eliciting a cascade of T cell response

9. • Viral reactivation
- Occurs in sequential fashion with HHV 6 and EBV, detected earlier in the course of the disease
 followed by HHV 7 and CMV.
- Either due to direct effect of drugs or metabolites on viral reactivation.
- Or due Drug induced immunosuppressed state characterized by hypogammaglolubulinaemia
causing initial reactivation of latent herpesvirus.
- Cytokine storm  due to anti drug immune response.
- Pro-inflammatory cytokines and chemokines, such as TNF-α, IFN-γ, IL-1, IL-2, IL-6, are seen in
lower levels in the early stage of the disease in patients with HHV-6 reactivation than in those
without HHV-6 reactivation.
- Number of plasmacytoid dendritic cells (pDCs), decreased in the blood and increased in the skin
around the time of viral reactivation  related to the reactivation of viruses.

10. Pathogenesis :

11. Clinical features
• Cardinal features include widespread skin lesion and systemic inflammation – fever, internal
organ involvement, lymphadenopathy and haemotological abnormalities.
• Long latent period of about 2 – 6 weeks between ingestion of drug and onset of symptoms.
• Prodromal phase of high grade fever 38 to 40 C, asthenia, malaise, fatigue, accompanied by
pharyngitis and cervical lymphadenopathy

12. Cutaneous manifestations :
• Presentations include
- Purpuric infiltrative urticarial papules and plaques (most common variant)
- Erythroderma
- Morbilliform eruption resembling measles
- Erythema multiforme like dusky or purpuric atypical target lesions
- Others - Polymorphic presentations like maculopapular, urticarial, exfoliative, lichenoid, pustular,
bullous, target-like, or eczema-like lesions

15. • Rash accompanied by facial edema is usually the first clinical feature to appear.
• Facial edema is the hallmark of the disease and might be due to vascular endothelial
growth factor pathway.
• Most noticeable at ears
• Mucosal lesions are frequently associated, with mouth and lips being the most commonly
involved
• Desquamation seen at the stage of resolution.

17. Systemic inflammation
• Lymphadenopathy – with enlargement of atleast 2 cm in diameter is considered to be
clinically significant.
• Early phase of DRESS syndrome may show decreased numbers of B lymphocytes with
hypoglobulinemia.
• Haematological abnormalities :
- Eosinophilia is most commonly seen in blood and tissue
- Atypical lymphocytosis
- Leucopenia
- Lymphopenia
- Thrombocytopenia

18. Hepatic manifestations
• Liver is the first most common organ to be affected and the damage can occur even before onset of
cutaneous lesions.
• Injury is more severe and is the primary cause of mortality in DRESS
• Liver injury is divided into 3 types based on ALT and ALP.
• Ratio of serum ALT results to ALP results with respect to their upper limits of normal range
(ULNs)
R = (serum ALT/ULNs of ALT)/(serum ALP/ULNs of ALP)
• Cholestatic type - R ratio less than 2 (MC)
• Hepatocellular type - R ratio greater than 5 (2nd mc)
• Mixed type - R ratio greater than 2 but less than 5

19. Renal manifestations :
• Risk factor for kidney injury – old age, underlying renal dysfunction and
cardiovascular disorders.
• Higher risk of kidney injury is with Allopurinol induced Dress.
• Proteinuria, haematuria, urinary eosinophils.
• Usually mild and will be recovered from in time without obvious sequelae. Rarely can
cause severe interstitial nephritis, acute tubular necrosis, or vasculitis, leading to
renal failure.
• Treatment includes hemodialysis in severe cases.

20. Pulmonary involvement
• Impaired pulmonary function
• Interstitial pneumonitis
• Pleuritis
• Acute respiratory distress syndrome
• Seen with usage of Minocycline

21. Cvs
• Linked with Minocycline, Sulfonamides and Ampicillin.
• Two forms : hypersensitivity myocarditis and acute necrotizing eosinophilic
myocarditis.
• Hypersensitivity myocarditis - mild and self-limiting.
• Acute necrotizing eosinophilic myocarditis is a more severe form of
hypersensitivity and with a high mortality rate of more than 50%
• Symptoms : Chest pain, dyspnoea
• On Examination : Tachycardia, Hypotension
• Echocardiogram, Ecg- T wave inversion, Elevated cardiac enzymes.

22. Nervous system
• Meningitis
• Encephalitis
Endocrine :
• Seen in later phase than the acute phase
• Thyroid gland, most frequently involved
• Both hypo and hyperthyroidism are seen
• Also can be associated with Alopecia areata

23. Common drugs causing dress syndrome
• Allopurinol
• Anti epileptics – Carbamazepine, Oxcarbamazepine, Phenytoin, Lamotrigene
• Antibiotics- Minocycline, Amoxycillin, Vancomycin
• Anti tuberculosis drugs
• Anti retroviral – Abacavir, Nevirapine
• Sulpha drugs – Dapsone, sulfasalazine, sulphadiazine
• Furosemide
• Omeprazole
• Ibuprofen, Acetominophen, Diclofenac

24. RegiSCAR DRESS scoring system
Clinical features Score
Rash >50% Body surface area 1 point
Rash suggestive of DRESS 1 point
Systemic involvement Maximum 6 points
lymphadenopathy, eosinophilia
atypical lymphocytosis,
organ involvement
Relevant negative serological tests 1 point
< 2 points – no case
2-3 point – possible case
4-5 point – probable case
> 5 point – definite case

25. Histology
• Spongiosis with focal subcorneal pustules
• Erythema multiforme-like interface dermatitis: basal vacuolar change and multiple
scattered apoptotic keratinocytes in the epidermis
• Lichenoid dermatitis: prominent infiltrations of cells in the upper dermis
• perivascular infiltration with prominent endothelial cells, red blood cell
extravasation, and some extent of vessel wall damage, resembling a feature of
lymphocytic vasculitis
• Leukocytoclastic vasculitis: fibrinoid necrosis, leukocytoclasia, and red blood cell
extravasation
• Superficial perivascular dermatitis.

27. Differential diagnosis
• Septicemia and viral infection
• Acute generalised exanthematous pustulosis – pustules are mainly flexural,
whereas in DRESS unlikely to be localised. Latency period of <5 days
• Erythema multiforme
• SJS/ TEN – Latency period of 7-10 days
• Acute severe eczema
• Psoriasis
• Cutaneous lymphoma
• Systemic vasculitis

28. Clinical course and prognosis
• Delayed onset and a prolonged and protracted evolution of the disease
• The duration of illness of DRESS syndrome is usually more than 15 days, with a
waxing-and-waning course with several flare-ups after recovery from initial
presentation.
• Risk factors for a prolonged evolution of the clinical course in DRESS syndrome –
increased baseline lymphocytosis, a higher value of liver enzyme levels, ethnicity,
and culprit drugs

29. Complications:
- Severe and life threatening : Fulminant hepatic failure, requiring transplant
- Mortality rate of 5-10%
• Delayed onset interstitial nephritis
• Interstitial pneumonitis
• Myocarditis
• Infections are the major complications due to treatment for DRESS syndrome,
including herpes labialis, herpes zoster, pneumonia, and soft tissue abscess - can
lead to septic shock and death
• Autoimmune disease may arise after DRESS- lupus erythematosus and
autoimmune thyroid disease

30. Investigations
• CBC
• LFT, Lactate dehydrogenase, Ferritin, Hepatitis B and C
• ECG, Echo, cardiac enzymes
• RFT, urine analysis, ultrasound
• CSF for culture and sensitivity, microscopy, CT/MRI head
• Chest Xray, PFT
• TFT
• Blood culture
• Amylase, Lipase, Triglycerides

31. Management
• Identify and eliminate the culprit drug
• Supportive measures
- Thermoregulation
- Iv fluids
- O2 supplementation
- Maintaining fluid balance
- Organ specific management

32. First line of management
• Oral corticosteroid - Prednisolone 0.5–1.0 mg/kg/day with a gradual tapering over
2–3 month.
• Failure to respond to oral prednisolone, iv is required- Methylprednisolone is
indicated.
• Methyl Prednisolone 1g/day for 3 days
Second line
- Intravenous immunoglobulin (IVIG) – can also cause severe adverse effects if used
as monotherapy

33. Third line :
- Cyclophosphamide
- Cyclosporine
- Mycophenolate mofetil
- Rituximab
- Valganciclovir – virus reactivation
- N acetyl cysteine for severe liver involvement
- ECMO – for cardiac insufficiency

34. References
• Rooks textbook of Dermatology 9th edition
• Iadvl
• Fitzpatrick’ dermatology 9th edition
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among
Drugs, Viruses, and Immune System - PMC [Internet]. [cited 2022 Oct 20]. Available
from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486066/
• Castellazzi ML, Esposito S, Claut LE, Daccò V, Colombo C. Drug reaction with eosinophilia
and systemic symptoms (DRESS) syndrome in two young children: the importance of an
early diagnosis. Italian Journal of Pediatrics. 2018 Aug 15;44(1):93.

35. Thank you