D.R.E.S.S. Syndrome  (Drug Reaction with Eosinophilia and Systemic Symptoms)

Condition is a very rare Type IV(b) adverse hypersensitivity reaction  to certain medications, with gradual onset,  on average about 32 days after a new medication. Can occur earlier or later.

Most common medications are anticonvulsants (phenytoin, carbamazepine, phenobarbital, levetiracetam, lamotrigine.  NSAIDS, B-Lactam antibiotics. Vancomycin, Allopurinol, TMP/SMZ.

INCIDENCE: About 1:10,000 of adverse cutaneous drug reactions, with a high mortality rate, if undiagnosed in the range of (3.8%-10%)

The rash is generalized morbilliform, but can be limited to the face, causing facial edema/erythema, mimicking erysipelas/angioedema.

CLINICAL FINDINGS:  Besides the rash, are fever, chills, malaise, pruritus and generalized lymphadenopathy, involving the cervical, axillary and inguinal lymph nodes. Can appear minimally ill or toxic, depending on stage of presentation.

Can cause multi-organ involvement, with liver being the most common target and as well as the kidneys.

Most common cause of death is due to hepatic necrosis with fulminant hepatitis and renal failure.

LABORATORY DATA: Eosinophilia > 6000x10(3)/uL. Thrombocytopenia/Pancytopenia. Leukocytosis Coagulopathy, elevated liver enzymes (ALT x 2 normal). Elevated BUN, proteinuria.

Above laboratory findings are indicators of poor prognosis!

DIAGNOSIS: High clinical suspicion. Should always be on the differential diagnosis of any erythematous rash, in patient on above medications.

DIFFERENTIAL DIAGNOSIS:  Steven-Johnson syndrome. Toxic epidermal necrolysis. Kawasaki disease, Hypereosinophilic syndrome. 

TREATMENT: Discontinue potential causative agent(s). Systemic corticosteroids (Prednisolone IV with gradual tapering. Cyclosporine IV, if no response or steroid contraindicated. Supportive care. Vigilant monitoring for potential multi-organ involvement.

 RS3PE SYNDROME (Remitting Seronegative Symmetrical Synovitis with Pitting Edema).

Clinical syndrome is a rare entity, often mimicking an infectious process.

Patients will present with unilateral or often bilateral abrupt onset of  painful, erythematous swelling 

of upper or lower extremities, associated with palpable pitting edema.

Usually afebrile, but mild temperature elevation can occur (secondary to the inflammatory process).

Generally, recurrent with increasing episodes of flare ups.  Patient often mistakenly treated with

antibiotics, with no significant improvement. Condition, generally abates spontaneously without

any therapy and  next flare up is treated with antibiotics, again. 

Thus, RS3PE can be undiagnosed for many months.

Epidemiology:  More common in patients greater then age 60, male>female, rural setting, rapid onset.

Frequently misdiagnosed as cellulitis, erythrodermatosis, RSD (reflex sympathetic dystrophy)

About 50% likelihood of undiagnosed underlying malignancy (prostate/breast/lung carcinoma).

Laboratory findings:  Elevated inflammatory markers (CRP/Sedimentation rate).

Mild leukocytosis.  Negative RF and Anti-CCP-Ab. 

Treatment: High index of clinical suspicion. 

Hint: Onset of abrupt bilateral cellulitis is extremely unlikely.

Low dose prednisone 10-20 daily, provides rapid improvement.

Remain vigilant for underlying undiagnosed malignancies!