Can Chronic Pain Develop After DRESS Syndrome?
Yes, chronic pain can develop after DRESS syndrome, though it is not a commonly emphasized sequela in the literature. The mechanisms that drive chronic pain in other inflammatory and immune-mediated conditions—including central sensitization, peripheral nerve injury, and prolonged immune activation—can theoretically occur following DRESS syndrome, particularly given its severe systemic inflammation, potential for nerve damage, and protracted clinical course.
Understanding the Biological Plausibility
Mechanisms That Support Chronic Pain Development
Peripheral nerve injury from inflammation: DRESS syndrome involves multi-organ inflammation and can cause nephritis, hepatitis, myocarditis, and other organ damage 1. When peripheral nerves are affected by inflammatory mediators or direct immune attack, neuropathic pain can emerge 2.
Central sensitization from prolonged inflammation: Chronic pain syndromes are associated with substantial functional and structural changes in the central nervous system, resulting from altered sensory and nerve function at every level of the nervous system 2. The prolonged inflammatory state in DRESS—which can last weeks to months and may relapse in approximately 12% of cases—creates conditions conducive to central sensitization 3, 4.
Viral reactivation and immune dysregulation: DRESS syndrome involves reactivation of herpes family viruses (particularly HHV-6, HHV-7, EBV, and CMV), against which the body mounts a strong immune response 5. This viral reactivation and prolonged T-cell immune activation can theoretically contribute to ongoing neuropathic pain, similar to post-herpetic neuralgia, which is a well-recognized chronic neuropathic pain condition following varicella zoster reactivation 2.
Denervation and nerve regeneration: Neuropathic pain can result from denervation or from the regeneration process itself, with "pathological pain" occurring in the absence of ongoing injury 2. If DRESS causes nerve damage during the acute phase, the subsequent regeneration or incomplete recovery could manifest as chronic pain.
Clinical Context and Risk Factors
Who Is at Risk?
Patients at highest risk of transitioning from acute to chronic pain include those with a history of any type of chronic pain, prior early-life adversity or trauma, poor coping styles such as catastrophizing, pre-existing anxiety and depression, or those who have had prior negative experiences with pain or recovery 2.
Psychological inflexibility, hypervigilance (constantly checking for pain), and pain catastrophizing are common in chronic pain syndromes and interfere with pain acceptance and response to treatment 2.
The presence of psychological comorbidity such as depression, anxiety, post-traumatic stress, or somatization interferes with pain processing and increases the likelihood of chronic pain development 2.
Specific DRESS-Related Factors
Severe organ involvement: Viral reactivation, severe internal organ involvement, and hematological abnormalities all portend a poorer prognosis in DRESS syndrome recurrence 4. These same factors may increase the risk of chronic pain through ongoing tissue damage and inflammation.
Prolonged or relapsing course: DRESS syndrome is characterized by a prolonged course, often with flares even after discontinuation of the causal drug 5. Relapse occurs in approximately 12% of cases, particularly with DRESS associated with viral reactivation 3, 4. This extended inflammatory period increases the window for chronic pain mechanisms to become established.
Inadequate immunosuppression: Premature steroid taper (less than the recommended minimum 4 weeks) increases relapse risk 1, 3. Relapsing inflammation may perpetuate pain pathways and increase the likelihood of chronic pain.
Types of Chronic Pain That May Develop
Neuropathic Pain
Neuropathic pain is described as a "cold burning pain" in a distribution that may be localized or diffuse, with increased painful response to light touch (allodynia) 2.
If DRESS causes peripheral nerve damage through inflammatory mechanisms or immune-mediated injury, patients may develop chronic neuropathic pain similar to other inflammatory neuropathies 2.
Musculoskeletal Pain
Musculoskeletal pain, including nonspecific pain and arthralgia, is common in chronic pain populations 2.
DRESS syndrome presents with constitutional symptoms including rigors, myalgias, and arthralgias 1, 6. If these symptoms persist beyond the acute phase, they may evolve into chronic musculoskeletal pain.
Complex Regional Pain Syndrome (CRPS)
CRPS usually follows an injury and is described as excruciating pain made worse by touch or stimulation, with sympathetic dysregulation playing a role 2.
While not specifically documented in DRESS literature, the severe inflammatory insult and potential for nerve injury could theoretically trigger CRPS in susceptible individuals.
Management Approach If Chronic Pain Develops
Early Recognition and Intervention
Monitor for pain beyond the acute phase: Clinicians should assess for persistent or new-onset pain during the prolonged steroid taper (minimum 4 weeks) and in follow-up visits after DRESS resolution 1, 3.
Screen for risk factors: Identify patients with prior chronic pain, psychological comorbidities, or poor coping styles early in the DRESS course 2.
Pain Management Algorithm
For neuropathic pain:
First-line agents include tricyclic antidepressants (low-dose) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which can be prescribed and managed by gastroenterologists or general practitioners 2.
Gabapentinoids (gabapentin, pregabalin) are also effective for neuropathic pain 2.
For musculoskeletal pain:
Management follows general population guidelines, including physical therapy, graded exercise programs, and judicious use of NSAIDs (if not contraindicated) 2.
Avoid opioids: Opioids should not be prescribed for chronic non-cancer pain, including pain following DRESS syndrome, due to risks of opioid use disorders, overdose-related deaths, and development of narcotic bowel syndrome 2.
For complex or refractory pain:
Multidisciplinary approach: Best outcomes are achieved with a multidisciplinary care team including a psychologist with experience in chronic pain 2.
Brain-gut behavior therapies: Cognitive behavioral therapy (CBT) is effective for patients with insight into how thoughts, feelings, and behaviors relate to pain 2. Hypnotherapy may benefit patients with visceral hypersensitivity or somatic symptoms 2.
Self-management strategies and neuromodulation: These are indicated when central mechanisms predominate 2.
Patient Education
Explain that pain is real and modifiable, and that peripheral factors can drive increased pain, but the brain processes and modulates sensory signals 2.
Use the Fear-Avoidance model to explain why some people have more pain than others despite similar diagnoses, and instill hope that a change in approach to pain could improve function 2.
Avoid pain catastrophizing language such as "you shouldn't be in so much pain" or continuing to order tests to find the "cause" of pain 2.
Common Pitfalls to Avoid
Premature steroid taper: Weaning systemic corticosteroids over less than 4 weeks increases relapse risk, which may perpetuate inflammation and increase chronic pain risk 1, 3.
Ignoring psychological factors: Failing to screen for and address anxiety, depression, catastrophizing, and poor coping styles will compromise pain management outcomes 2.
Prescribing opioids: Opioids are ineffective and potentially harmful for chronic non-cancer pain and should not be used 2.
Overlooking rehabilitation: Arranging a rehabilitation program with physiotherapy and occupational therapy is crucial for recovery and can reduce the risk of chronic pain through graded exercise and restoration of function 2.