Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome, is a serious, sometimes lethal, immunological reaction to drug metabolites involving multiple organ systems. Some of the common causative agents of DRESS include allopurinol, minocycline, sulfasalazine, azathioprine, antiepileptic drugs, and hydroxychloroquine. DRESS is often misdiagnosed and challenging to clinically manage due to the disease’s myriad presentations, acute complications, and long-term sequela after initial resolution. We present the case of a 39-year-old female patient that developed type 1 diabetes as a sequela of DRESS. The patient originally presented to the emergency department with three days of fevers and a pruritic erythematous maculopapular rash that began two weeks prior. She had recently started an antibiotic course and had also been on a long-term antiepileptic drug regimen. Following a thorough clinical examination, the patient was diagnosed with DRESS and treated accordingly. Over the next four months, she went on to have multiple hospitalizations with several admissions to the medical intensive care unit. She had numerous complications including significant facial edema, seizures, bacterial pneumonia, sepsis, hypovolemic shock, acute respiratory distress syndrome, diabetic ketoacidosis, nonalcoholic steatohepatitis, liver failure, and recurring DRESS rashes despite treatment with high-dose intravenous steroids and immunosuppressants. During this time, the patient developed a rare form of uncontrolled type 1 diabetes mellitus not explained by autoantibody production or continued high-dose steroid use. Fulminant type 1 diabetes mellitus is a sequela of DRESS that is poorly understood and rarely reported. When it occurs, it significantly and negatively affects patient prognosis and requires careful monitoring to assure proper glycemic control.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DIHS), is a serious, sometimes lethal, immunological reaction to drug metabolites involving multiple organ systems [
A 39-year-old African American female with a medical history of chronic focal epilepsy presented to Stony Brook University Hospital emergency department with three days of fevers (>38°C) and mildly pruritic erythematous maculopapular rash. The rash began two weeks prior in the left arm and gradually spread bilaterally to the trunk, face, oropharynx, periocular space, and legs (Figure
Patient’s forearms four weeks following the original erupting rash. Pictured here are follicular erythematous papules with scattered postinflammatory hyperpigmented macules becoming confluent in areas with desquamation. This pattern persisted bilaterally in the trunk and upper and lower extremities.
The patient’s initial laboratory studies showed an elevated neutrophil count (10.47 K/ul), mild eosinophilia (6–8%), and transaminitis (AST : 48 IU/L; ALT : 42 IU/L). Initial evaluation by the dermatology service suggested a differential diagnosis of AGEP secondary to amoxicillin versus DIHS secondary to lamotrigine or carbamazepine use. A computed tomography (CT) scan revealed no clear etiology of infection, blood cultures were negative, skin cultures from pustules only grew normal skin flora, and skin biopsy revealed nonspecific findings most consistent with AGEP (Figure
Low-power microscopy images of the patient’s skin biopsy (40x and 100x) show interface dermatitis with focal spongiotic dermatitis. On the high-power image, (400x) there is vacuolar interface dermatitis (lymphocytes tagging along the dermoepidermal junction) and rare necrotic keratinocytes within the epidermis. The histopathologic changes are nonspecific but can be observed in drug eruption reactions.
Approximately, a month following onset of the rash, the patient’s serum glucose was found to be over 500 mg/dL with a hemoglobin A1C of 7.1% without a prior history of diabetes mellitus (DM). The patient was started on insulin therapy for probable steroid-induced diabetes mellitus (SIDM), as she was requiring a high-dose steroid regimen for DRESS. The patient’s SIDM was complicated by DKA during a sepsis episode precipitated by a bacterial pneumonia. She remained in the MICU for several weeks where she was managed with respiratory support, antibiotics, insulin, and steroids. She was eventually discharged from the hospital following improvement of her respiratory status, sepsis, liver failure, DRESS rash, and serum glucose levels. The steroids were tapered off during outpatient follow-up, and her SIDM briefly improved. However, despite continuing a steroid taper, she had significant fluctuating fasting glucose levels and her insulin regimen was titrated. The patient continued to have persistently elevated serum glucose levels (>300 mg/dL) requiring insulin therapy despite cessation of steroids. She required multiple daily insulin injections and wore a continuous glucose monitoring device (CGM). Glutamic acid decarboxylase (GAD) antibodies and islet cell cytoplasmic autoantibodies (ICAs) were tested for correlation with autoimmune subtype of type 1 DM; however, they were found to be negative. The patient’s new onset uncontrolled type 1 DM was originally diagnosed as SIDM, which normally improves following reduction or cessation of steroids. However, given her worsening glycemic control in the context of tapering and short-term cessation of steroids, the patient was diagnosed as having a rare but previously documented type of fulminant type 1 DM as a sequela of DRESS [
DRESS syndrome is a clinically significant skin phenomenon with systemic involvement within the SCARs phylogeny of cutaneous immune responses to drug exposure. DRESS can be lethal with a mortality rate approaching 10% and is believed to occur with an incidence ranging from 1 : 1000 to 1 : 10,000 drug exposure, although exact incidence is unknown and may vary by population [
The patient’s early presentation was classic of DRESS syndrome, with lymphadenopathy, facial edema, erupting morbilliform rash, fevers, and liver and spleen involvement. It is worth noting that she initially had mild transaminitis, which quickly progressed to significant transaminitis and near liver failure; thus, the original liver enzyme values are not necessarily prognostic of disease progression. Nevertheless, liver involvement is highly correlated with DRESS and found to occur as high as 87% of DRESS patients [
It is not fully clear what agent induced DRESS syndrome in this case presentation. The patient had been on long-term carbamazepine treatment for epilepsy, had begun lamotrigine a few months prior, and just initiated a course of amoxicillin.
The patient’s hyperglycemia was first noted in outpatient setting about a month following the original DRESS rash. As the patient had been on an intensive steroid and immunosuppressant treatment regimen for DRESS, the globally elevated hyperglycemia was believed to be SIDM. SIDM is an expected outcome of long-term medical glucocorticoid use. The prognosis for SIDM is generally positive; once the steroid dosing is reduced, insulin requirements decrease, and normal endocrine function is reestablished [
Nonautoimmune fulminant type 1 DM as a development from DRESS is uncommon and has been scarcely reported. A previous study by Chen et al. found 1 in 43 patients with fulminant type 1 DM 1-2 months post-DRESS [
Fulminant type 1 DM as a sequela of DRESS is a poorly understood and rarely reported clinical phenomenon. When it occurs, it significantly and negatively affects the prognosis and requires a constant, careful, and financially costly management of these patients to assure proper glycemic control. Earlier identification of this chronic complication of DRESS will aid clinicians in more efficient treatment that will improve patient outcomes. Clearly, more work is needed to further elucidate the physiology underlying this unique pathology.
The authors declare that they have no conflicts of interest.