SDRIFE (Symmetrical Drug-Related Intertriginous and Flexural Exanthema) is a rare cutaneous adverse drug reaction associated with systemic medications. It is caused by specific drugs including broad-spectrum antibiotics and cephalosporins.
The disease was initially called “baboon syndrome” when first reported in 1984, named after the characteristic erythema appearing on the buttocks and perianal area. The current name “SDRIFE” has become established as a more accurate description of the condition.
The diagnosis of SDRIFE requires fulfillment of all five of the following criteria.
Since the first report in 1984, over 100 cases have been reported in the literature. It occurs in patients of all ages, with reports ranging from 18 months to 84 years. Onset in children is rarer. The male-to-female ratio is approximately 3:1, with a predominance in males.
Since its first report in 1984, this is a rare disease with only over 100 cases reported in the literature. The male-to-female ratio is approximately 3:1, with a predominance in males. It can occur at any age, but is even rarer in children.
The drugs that cause SDRIFE are listed below.
| Classification | Main Drugs |
|---|---|
| Beta-lactam antibiotics | Amoxicillin, cephalosporins |
| Non-beta-lactam antibiotics | Clindamycin, co-trimoxazole |
| Antiviral drugs | Valacyclovir |
| Ophthalmic drugs | Acetazolamide, broad-spectrum antibiotics |
Beta-lactam antibiotics, especially amoxicillin, are the most common causative drugs.
Acetazolamide is widely used in ophthalmology as a first-line treatment for idiopathic intracranial hypertension (IIH), but it is known to cause maculopapular eruptions. Metabolites produced after hepatic metabolism act as haptens, triggering a T-cell-mediated immune response that leads to skin reactions.
Broad-spectrum antibiotics used to treat ocular infections can also cause SDRIFE. Ophthalmologists need to be aware of the potential cutaneous complications of the drugs they prescribe.
SDRIFE can occur with acetazolamide (first-line treatment for IIH) and broad-spectrum antibiotics used for eye infections. Acetazolamide metabolites after hepatic metabolism act as haptens, triggering a T-cell-mediated immune response.
The diagnosis of SDRIFE is primarily based on clinical diagnostic criteria. For detailed diagnostic criteria, refer to the section “What is SDRIFE?”.
Differential diagnosis from the following diseases is necessary.
A skin biopsy may be performed to aid in the definitive diagnosis. The main histological findings are shown below.
Consultation with a dermatologist is recommended for differential diagnosis and treatment.
Clinical Diagnosis
Five clinical criteria: Confirm all of the following: exposure to systemic medication, buttock erythema, involvement of additional intertriginous areas, symmetry, and absence of systemic toxicity.
Detailed history: Obtain a thorough history of medication use, onset, and distribution of symptoms.
Ancillary Tests
Histological examination: Performed as an aid to definitive diagnosis. Various findings from superficial perivascular inflammatory infiltration are confirmed.
Dermatology consultation: Recommended for differential diagnosis and determination of treatment strategy.
The first step in treatment is a risk-benefit analysis of the drug that caused the skin reaction. The decision is made by comparing the severity of the skin reaction with the therapeutic benefit provided by the drug.
If risk-benefit analysis determines that discontinuation of the causative drug is necessary, consider alternative medications. Treatment decisions should be individualized based on patient-specific factors and the risk-benefit profile of each drug.
Non-pharmacological approaches (diet, weight loss, aerobic exercise) may also be considered to alleviate symptoms of eye disease. A multidisciplinary team approach should be used to develop a management plan, and comorbidities should also be assessed.
The following treatments are performed under consultation with a dermatologist.
After discontinuing the causative drug and monitoring the effect, re-administration under strict supervision may be considered. While gradually increasing the dose, monitor both signs of skin rash and signs of ocular disease (changes in intraocular pressure and fundus examination) simultaneously.
A risk-benefit analysis is necessary, weighing the severity of the skin reaction against the therapeutic benefit. For drugs essential to IIH treatment, such as acetazolamide, particularly careful judgment is required; avoid self-discontinuation and always consult your physician.
SDRIFE is caused by a type IV (delayed-type) allergic reaction. The rapid onset of the rash is thought to be due to the drug directly binding to T-cell receptors.
Histological examination reveals dermal infiltration characterized by CD3+ and CD4+ T cells. This is accompanied by expansion of CD26 P-selectin. CD26 P-selectin is normally involved in recruiting memory or effector Th1 cells (type 1 helper T cells) to the site of inflammation, and its expression is increased in the endothelial and keratinocyte layers.
Acetazolamide is metabolized in the liver and converted into metabolites, which act as haptens to trigger a T-cell-mediated immune response, leading to skin reactions.
Although not fully understood, the immune response selectively occurs in the skin of intertriginous and flexural areas. Specifically, reactions occur in the axillae, gluteal cleft, antecubital fossae, and popliteal fossae. Further research is needed on the mechanism of this selectivity.
Although not fully understood, it is thought to be due to a T-cell-driven immune response that selectively migrates to intertriginous and flexural areas (axillae, gluteal cleft, cubital fossa, popliteal fossa). The mechanism of this selectivity is still under investigation.
