Published: 1 September 2022


Re-ad-DRESS-ing the risk of DRESS with cautious titration

Prescriber Update 43(3): 38–40
September 2022

Key messages

  • Drug reaction with eosinophilia and systemic symptoms (DRESS) is a serious medicine-induced hypersensitivity reaction.
  • Antiepileptic medicines, antibiotics and allopurinol are most frequently associated with DRESS.
  • Titrate these medicines when commencing treatment to decrease the risk of DRESS.

The Centre for Adverse Reactions Monitoring (CARM) recently received a case report (CARM ID: 143028) of a patient who was started on allopurinol and developed drug reaction with eosinophilia and systemic symptoms (DRESS) and subsequently Stevens-Johnson syndrome (SJS).


DRESS is a serious, potentially life-threatening medicine-induced hypersensitivity reaction. This reaction is characterised by an extensive skin rash, visceral organ involvement, lymphadenopathy, eosinophilia and atypical lymphocytosis.

Most cases of DRESS have a clear medicine exposure. Pharmacogenetic studies have also identified an association between the risk of DRESS and several human leukocyte antigen (HLA) haplotypes and genetic variants.

Most patients recover from DRESS following cessation of the offending medicine. However, recovered patients are at risk of long-term autoimmune sequelae. DRESS can also be fatal, with a mortality rate between 2 and 10 percent. Severe organ involvement and multiorgan failure are the leading causes of death in DRESS patients.

Importance of titration

Titration involves changes to medicine doses to achieve the best clinical response at the lowest dose possible, with the intention of reducing unnecessary medicine use and adverse events.2 There is indirect evidence that the risk of DRESS for certain medicines is dose-dependent.1 For example, a review of DRESS cases induced by phenytoin has identified delayed phenytoin clearance and accumulation.1

High starting doses and rapid titration rates contribute to the risk of adverse effects such as DRESS.3 Therefore, starting treatment with a low dose and gradual titration may decrease this risk.3 Additionally, the latency between medicine initiation and the onset of DRESS is prolonged, typically between two to eight weeks.1,4 A slow drug titration may allow more time to notice and diagnose early symptoms of DRESS.

Common offenders

Antiepileptics (carbamazepine, phenytoin, lamotrigine), allopurinol, vancomycin and sulfonamide-containing antibiotics are commonly associated with DRESS.1 Refer to the medicine data sheets for information about the risk of DRESS and how to manage it.

Search for a data sheet


When commencing allopurinol treatment for gout, start with a low dose and then gradually increase it until the serum urate target is achieved.5 The medicine may be used long-term but must be stopped if a rash or other signs of allergy appear.5

The excretion of allopurinol and its metabolites is prolonged in patients with renal impairment.5 Therefore, doses may be halved or reduced even further when beginning therapy and then slowly increased depending on patient response.5,6 Additionally, renal impairment has an additive effect to genetic predisposition on the risk of allopurinol-induced DRESS and other severe cutaneous adverse reactions.1


Skin rash is a common adverse effect of lamotrigine and is likely to occur within the first eight weeks of treatment.7 Skin rashes are usually mild, but may develop into a severe skin reaction in rare cases.7 Lamotrigine-induced DRESS has been reported and is a well-known example of the relationship between dose, titration rate and rash.3 When initiating lamotrigine treatment, it is important to start low and titrate slowly, as high initial doses or a rapid dose escalation increases the risk of severe adverse effects such as DRESS.7–9


DRESS has also been reported in patients taking phenytoin. Individualise the dose of phenytoin to obtain maximum benefit for the patient. Increase the dose at two-weekly intervals.

New Zealand case reports

Up until 17 June 2022, CARM had received 132 reports of DRESS. Some reports had more than one suspect medicine. The most frequently reported suspect medicines were allopurinol, vancomycin, carbamazepine and trimethoprim-sulfamethoxazole (Table 1). The data sheets for these medicines include warnings for DRESS.

Table 1: Suspect medicines* and number of DRESS reports

Suspect medicine Number of DRESS reports
Allopurinol 37
Vancomycin 13
Carbamazepine 12
Trimethoprim-sulfamethoxazole 9
Amoxicillin 8
Piperacillin-tazobactam 8
Flucloxacillin 6
Lamotrigine 5

* The table only shows suspect medicines with 5 or more reports of DRESS.

Source: Centre for Adverse Reactions Monitoring


  1. Lee H. 2020. Drug reaction with eosinophilia and systemic symptoms (DRESS). In: UpToDate 8 December 2020. URL: (accessed 15 July 2022).
  2. Caffrey AR and Borrelli EP. 2021. The art and science of drug titration. Therapeutic Advances in Drug Safety 11(Jan 19): 2042098620958910. DOI: 10.1177/2042098620958910 (accessed 8 August 2022).
  3. Seiden LG and Connor GS. 2022. The importance of drug titration in the management of patients with epilepsy. Epilepsy & Behavior 128(March): 108517. DOI: (accessed 20 July 2022).
  4. Rademaker M and Oakley A. 2016. Drug hypersensitivity syndrome January 2016. URL: (accessed 15 July 2022).
  5. Douglas Pharmaceuticals Ltd. 2021. DP-Allopurinol New Zealand Data Sheet 31 March 2021. URL: (accessed 14 July 2022).
  6. Waitemata District Health Board. 2019. SafeRX – Allopurinol Safer Prescribing - Dose Up reviewed March 2022. URL: (accessed 15 July 2022).
  7. GlaxoSmithKline NZ Limited. 2021. Lamictal New Zealand Data Sheet 18 May 2021. URL: (accessed 15 July 2022).
  8. Waitemata District Health Board. 2016. SafeRX - Lamotrigine Safe Prescribing - Does the Dose Fit Reviewed August 2019. URL: (accessed 15 July 2022).
  9. Ponen S. 2022. Lamotrigine In: Health Navigator 13 June 2022. URL: (accessed 15 July 2022).
  10. Viatris Ltd. 2022. Dilantin New Zealand data sheet 4 May 2022. URL: (accessed 15 July 2022).
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