Hypersensitivity Syndrome (HSS) is a severe, unpredictable reaction to a medication that can become life-threatening if not quickly recognized. It is often referred to by the acronym DRESS, which stands for Drug Reaction with Eosinophilia and Systemic Symptoms. HSS represents a form of severe cutaneous adverse reaction (SCAR). The syndrome is not a typical immediate allergic response but rather a delayed immune system overreaction that demands immediate medical attention.
Defining Hypersensitivity Syndrome (HSS) and Its Triggers
HSS is an immune-mediated disorder distinguished by its delayed nature, contrasting sharply with immediate allergic reactions like anaphylaxis. The mechanism involves an overactivation of the body’s T-cells, which are a type of white blood cell. These T-cells mistakenly target the body’s own tissues in response to the drug or its metabolites.
Onset typically occurs between two and eight weeks after a patient begins taking the new medication, though it can sometimes take up to three months. This significant delay often complicates the process of identifying the drug responsible for the reaction.
Several classes of medications are frequently implicated in triggering HSS. Anticonvulsant drugs, such as carbamazepine, phenytoin, and phenobarbital, are common culprits, with an estimated incidence of one in every 10,000 patients exposed. The anti-gout medication allopurinol and certain antibiotics, particularly the sulfonamides, are also strongly associated with this severe reaction.
The development of HSS is not solely dependent on drug exposure; genetic susceptibility plays a significant role. Specific human leukocyte antigen (HLA) types increase a person’s risk when taking certain medications. Additionally, HSS often involves the reactivation of latent herpesviruses, such as Human Herpesvirus 6 (HHV-6), which may contribute to the severity and long-lasting nature of the syndrome.
Recognizing the Delayed and Diverse Signs
The clinical presentation of Hypersensitivity Syndrome is generally described by a triad of symptoms: a persistent fever, a widespread skin rash, and evidence of internal organ involvement. The fever is often the earliest sign, characteristically high and unexplained by any other infection, frequently preceding the appearance of the rash by several days. This high temperature signals the systemic nature of the immune activation.
The skin rash associated with HSS is highly variable, ranging from a mild, measles-like (morbilliform) eruption to a severe, blistering, or exfoliating condition. Rashes may begin on the face or upper torso before spreading, and facial swelling is common. The skin changes can also involve mucosal surfaces, such as the mouth, lips, or genitalia, although this is less frequent than in other severe skin reactions.
The most concerning aspect of HSS is the involvement of internal organs, which can progress independently of the rash’s severity. The liver is the most commonly affected organ, with inflammation (hepatitis) and elevated liver enzymes detected in blood tests. Kidney dysfunction (nephritis) and lung inflammation (pneumonitis) are also frequently reported complications.
Enlargement of the lymph nodes (lymphadenopathy) is another typical sign, reflecting the widespread immune system activation. The damage to these internal organs can lead to life-threatening complications. If the causative drug is not stopped immediately upon symptom recognition, the condition can progress and result in multi-organ failure.
Diagnosis and Treatment Protocols
Diagnosing Hypersensitivity Syndrome relies on a comprehensive clinical assessment because no single laboratory test can definitively confirm the condition. A diagnosis is strongly suspected when the patient presents with the characteristic combination of fever, a widespread rash, and the delayed onset of symptoms following the start of a new medication, typically within the 2-to-8-week window.
Blood tests are crucial for supporting the clinical suspicion and assessing the extent of internal damage. A common finding is eosinophilia, which is an abnormally high count of eosinophils, a specific type of white blood cell, in the bloodstream. Additionally, blood work will often reveal elevated liver enzymes, indicating liver inflammation, and markers of kidney dysfunction.
The cornerstone of HSS management is the immediate and permanent withdrawal of the suspected triggering medication. Identifying the culprit drug is the single most important action to prevent the progression of organ damage. All other medications that are not absolutely necessary are often stopped as well, in case a different agent is contributing to the reaction.
Treatment protocols primarily focus on supportive care, often requiring hospitalization to monitor for organ failure and manage symptoms. For severe cases involving significant internal organ inflammation, systemic corticosteroids, such as prednisone, are frequently administered to suppress the excessive immune response. While their use is widespread, the benefit of corticosteroids in HSS is not definitively established by controlled clinical trials, and they must be tapered slowly to prevent a relapse of symptoms.
Patients who have experienced HSS must be educated to avoid the causative medication for life, and they should be aware of the potential for cross-reactivity with chemically similar drugs. Long-term follow-up is necessary due to the possibility of a delayed onset of autoimmune disorders, which can occur months or even years after the initial episode has resolved.