Case Report

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www. elsevier. com/ locate/ajem

American Journal of Emergency Medicine 34 (2016) 764.e1-764.e3

Seventeen-year-old sexually active male with rash?

Drug Reaction with Eosinophilia and Systemic Symptoms syndrome is a fairly rare but potentially life-threatening Adverse drug reaction characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and multiorgan involvement. Pathogenesis of the disease is not fully understood, but proposed mechanisms include drug metab- olism defects, human herpesvirus reactivation, and genetic predisposi- tion. Diagnosis and treatment can be difficult or even delayed, as there are no globally accepted diagnostic criteria and those afflicted have non- specific clinical findings. There are several drugs well known to produce DRESS syndrome, although Bactrim is not normally thought of as a causative agent. We present the case of a 17-year-old male with high- risk sexual behavior who presented to the pediatric emergency depart- ment (ED) with rash and fever, first thought to have symptoms related to sexual history, but was instead diagnosed with DRESS syndrome due to sulfamethoxazole ingestion. This is the only case in the ED literature that describes sulfamethoxazole-induced DRESS syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a fairly rare but potentially life-threatening adverse drug reaction characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and multiorgan involvement. It often has a relapsing and remitting course [1]. The exact incidence is estimated to occur between 1 in 1000 and 1 in 10 000 drug exposures [1,2]. Although numerous medications can be the culprit, aromatic anticonvulsants are the most commonly reported cause of DRESS [1]. Other culprit drug categories include antidepressants, sulfonamides and sulfones, Anti-inflammatory agents, antibiotics, angiotensin-converting enzyme inhibitors, and ?-blockers [3].

A 17-year-old previously healthy male with a significant history of high-risk sexual behavior presented to our pediatric emergency depart- ment (ED) with complaints of fever, joint pain, and rash of 4 days dura- tion. He also complained of swelling of his penile foreskin, nonbloody diarrhea, a sore throat, cough, nausea/vomiting, abdominal pain, and diffuse myalgia. Of note, the patient had a history of Sexual activity with more than 25 males and had received treatment for gonorrhea 1 week before presentation. He had also been using trimethoprim/sulfa- methoxazole for treatment of facial acne for 1 month. On admission, the patient was found to be febrile to 100.3?F. Examination was remark- able for facial edema, papules on the buccal mucosa, and rash over the entire body surface. Scattered tender lymphadenopathy, abdominal tenderness upon palpation of the right upper quadrant, pain and limited of range of motion in several joints, and mild swelling of the penile fore- skin were also appreciated. Workup ensued due to initial concerns for

? Funding: No funding sources.

acute HIV infection, secondary syphilis, disseminated gonorrhea, auto- immune or infectious hepatitis, and rheumatic fever.

Laboratory test results during hospitalization were remarkable for the following: leukocytosis, elevated absolute Neutrophil count, abso- lute lymphocytosis, absolute eosinophilia, elevated bilirubin and liver function tests, elevated creatinine, and elevated C-reactive protein and erythrocyte sedimentation rate. An extensive panel of laboratory tests for viral and bacterial infections was negative. Ultrasound demonstrated hepatosplenomegaly, diffuse gallbladder wall thickening, prominent lymph nodes in the porta hepatis/pancreatic head, and small bowel as- cites. Dermatology was consulted and noted the following: generalized edema most prominent in the face; diffuse, erythematous, macular rash on the face, trunk, and upper extremities including the palms; viola- ceous discoloration on the face with some mild desquamation and mild honey-colored crusting in the ears; and discrete, 1 to 2 mm cobble- stone, flesh-colored to slightly erythematous papules on the dorsal hands and arms, trunk, and abdomen (Figs. 1-3). No targetoid plaques or bullae were noted. Nikolsky sign was absent.

Drug reaction with eosinophilia and systemic symptoms syndrome often begins with a prodrome of pruritus and high-grade fever (38?C- 40?C), after which the other classical findings develop in a relapsing and remitting pattern for weeks to months, even after withdrawal of the caus- ative agent [1-3]. There are various cutaneous manifestations, but the most common is a diffuse morbilliform rash [1]. Significant facial swelling is also very suggestive of DRESS, and mucous membranes involvement is common [1-4]. The skin rash may progress to a violaceous color with dif- fuse scaling that can remain for weeks to month after initial presentation [1,2]. Multiorgan involvement is seen in severe cases of DRESS syndrome. Tender lymphadenopathy is usually found along with marked leukocyto- sis, atypical lymphocytes on smear or biopsy, eosinophilia, thrombocyto- penia, and anemia with development of Hemophagocytic Syndrome [1,2,4]. The liver is the most commonly affected visceral organ; if untreat- ed, DRESS has an estimated mortality rate of 10% to 20% with the most common cause of death being hepatic necrosis [1,3-5].

Because DRESS can be mimicked by many other illnesses, a broad differential must be considered. Confounding our patient’s presentation was a history of high-risk sexual activity. Furthermore, several disease manifestations may mimic DRESS syndrome symptoms, including acute HIV infection, systemic gonoccocal infection, secondary syphilis, human herpesvirus infections, hepatitis infections, influenza, and Stevens-Johnson syndrome/toxic epidermal necrolysis [6-10].

There are no globally accepted diagnostic criteria for DRESS; thus, a High clinical suspicion for the illness is paramount. The first and most important management step in DRESS is the identification and with- drawal of the causative agent [2,5]. Supportive therapy with antipy- retics and topical steroids to ease symptoms as well as Fluid replacement, correction of electrolyte abnormalities, high caloric intake,

0735-6757/(C) 2015

764.e2 A. Boyd et al. / American Journal of Emergency Medicine 34 (2016) 764.e1–764.e3

Fig. 3. Diffuse erythematous, macular rash on the upper extremity on day 3 of hospitalization.

Fig. 1. Prominent facial edema on day 3 of hospitalization.

and dressings for the skin are all typical interventions [5]. In severe cases or in those cases that do not improve after the administration of system- ic corticosteroids, intravenous immunoglobulin should be considered [2,4,5].

The patient’s presentation supported a diagnosis of DRESS syn- drome. Skin biopsy demonstrated mixed features of spongiotic and in- terface dermatitis with intense perifollicular inflammation, consistent with a drug eruption. Etiology was thought to be due to sulfonamide an- tibiotic use. The patient was started on oral prednisone 1 mg/kg per day, rapid improvement was noted, and the patient was discharged on a 6- week taper with dermatology follow-up. He recovered with normaliza- tion of laboratory test results and a complete wean off corticosteroids in 8 weeks. Our case demonstrates the need to consider a broad differen- tial diagnosis in the ED while reinforcing the importance of multidisci- plinary involvement in the management of complicated systemic presentations.

Fig. 2. Cobblestone flesh-colored to slightly erythematous papules on the dorsal hand on day 3 of hospitalization.

Anne Boyd¹

University of Minnesota Medical School, Minneapolis, MN 55455

E-mail address: [email protected]

David Mills, MD? University of Minnesota Pediatrics Residency Program, Minneapolis, MN 55454

Corresponding author at: 2450 Riverside Avenue, Minneapolis, MN 55454. Tel.: +1 612 672 6000; fax: +1 612 273 4069.2450 Riverside

AvenueMinneapolisMN55454

E-mail address: [email protected]

Kristen Hook, MD² Pediatric Dermatology, University of Minnesota Masonic Children’s Hospital, Minneapolis, MN 55454 E-mail address: [email protected]

Rahul Kaila, MD² Pediatric Emergency Medicine, University of Minnesota Masonic Children’s Hospital, Minneapolis, MN 55454

E-mail address: [email protected]

¹ Tel.: +1 612 273 3000; ² Tel.: +1 612 672 6000; fax: +1 612 273 4069

http://dx.doi.org/10.1016/j.ajem.2015.08.043

References

1. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part I. clinical perspectives. J Am Acad Dermatol 2013;68(5):693.e1-693.e14. http://dx.doi.org/10.1016/j.jaad.2013.

   01.033 [quiz 706-8].

   Fernando SL. Drug-reaction eosinophilia and systemic symptoms and drug-induced hypersensitivity syndrome. Australas J Dermatol 2014;55(1):15-23. http://dx.doi. org/10.1111/ajd.12085.

2. Criado PR, Avancini J, Santi CG, Medrado AT, Rodrigues CE, de Carvalho JF. Drug re- action with eosinophilia and systemic symptoms (DRESS): a complex interaction of drugs, viruses and the immune system. Isr Med Assoc J 2012;14(9):577-82.
3. Descamps V, Ranger-Rogez S. DRESS syndrome. Joint Bone Spine 2014;81(1):15-21. http://dx.doi.org/10.1016/j.jbspin.2013.05.002.
4. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part II. Management and ther- apeutics. J Am Acad Dermatol 2013;68(5):709.e1-9. http://dx.doi.org/10.1016/j. jaad.2013.01.032 [quiz 718-20].
5. Tattevin P, Camus C, Arvieux C, Ruffault A, Michelet C. Multiple organ failure during primary HIV infection. Clin Infect Dis 2007;44(3):e28-9 [doi:CID41052 [pii]].
6. Holmes KK, Counts GW, Beaty HN. Disseminated gonococcal infection. Ann Intern Med 1971;74(6):979-93.
   

   Boyd et al. / American Journal of Emergency Medicine 34 (2016) 764.e1–764.e3 764.e3

7. Read P, Abbott R, Pantelidis P, Peters BS, White JA. Disseminated gonococcal infec- tion in a homosexual man diagnosed by nucleic acid amplification testing from a skin lesion swab. Sex Transm Infect 2008;84(5):348-9. http://dx.doi.org/10.1136/ sti.2008.030817.
8. Baum EW, Bernhardt M, Sams Jr WM, Alexander WJ, McLean GL. Secondary syphillis. Still the great imitator. JAMA 1983;249(22):3069-70.
9. Mattei PL, Beachkofsky TM, Gilson RT, Wisco OJ. Syphilis: a reemerging infection. Am Fam Physician 2012;86(5):433-40 [doi:d10229 [pii]].