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Angela D. Shedd, medical Acute onset of rash student, Suraj G. Reddy, MD, Jeffrey J. Meffert, MD, Richard P. Usatine, MD, and and Eric W. Kraus, MD Division of Dermatology and Cutaneous Surgery, 29-year-old man sought treatment scaly, and erythematous plaques covering University of Texas Health at our clinic for an extensive rash his entire scalp (FIGURE 1). The patient’s Science Center at San Antonio Ahe’d developed the month before. conjunctiva and oropharynx were clear. ed i t o r The rash was on his scalp, umbilicus, His fingernails showed hyperkeratosis, Richard P. Usatine, MD University of Texas Health glans penis, palms, and soles of his feet. subungual debris, and nail fold erythe- Science Center at San Antonio He reported swelling in his left and ma, without pitting. He also had bilat- his fourth toes bilaterally that was exac- eral swelling of the distal interphalangeal erbated by weight bearing. During the joints of his index fingers. 2 days prior to his visit to the clinic, the The patient’s umbilicus had a scaly patient said he’d had a fever and night erythematous plaque, while there were sweats; he denied ocular symptoms, GI confluent erythematous plaques in the complaints, , or penile discharge. groin area, and on the glans penis. There When asked about his sexual history, were also similar erythematous plaques in the patient noted that he’d had unpro- the axilla and inguinal folds; plaques on tected intercourse with a woman a year the lower extremities had a thicker layer earlier that resulted in on urination of scale. The patient’s feet had crusted fast track and resolved on its own. Other than a re- plaques on the plantar surface, hyperker- solved case of oral thrush, the patient had atotic nails with thick subungual debris, During the 2 days a noncontributory past medical history, and swelling and tenderness of the fourth prior to his took no medications, and had no family toes bilaterally (FIGURE 2). visit, he’d had history of . A physical exam revealed circinate, z What is your diagnosis a fever and night sweats; he denied ocular symptoms f ig u r e 1 f ig u r e 2 or dysuria Circinate plaques Hyperkeratotic nails, swollen toe

A 29-year-old man with circinate plaques on his scalp. The patient had subungual hyperkeratosis, , and of the fourth toe.

www.jfponline.com vol 56, No 10 / October 2007 811 ds n rou z Diagnosis: ten appear elsewhere on the body. On the Reiter’s syndrome uncircumcised penis, these shallow ulcer- This young man had Reiter’s syndrome ations have a micropustular, serpiginous photo (RS), a form of reactive that border and are referred to as comprises a small subset of cases within circinata. However, they may also appear the larger family of rheumatoid factor- psoriasiform in nature on circumcised seronegative spondyloarthritides—con- men, as was the case with our patient. ditions noted primarily for Coincident findings include onychol- of the axial skeleton.1 ysis and subungual hyperkeratosis, le- Of historical interest is the fact that sions mimicking migratory glossitis, and this diagnosis shares its name with the anterior . man who first described it, , a Nazi physician who tested unapproved vaccines and performed experimental z The typical patient? procedures on victims in concentration A young, white man camps. The infamous legacy of Reiter’s Patients with RS are almost always Cau- name has led to the proposal that the casian males in their early twenties and syndrome be referred to by another, are typically HLA-B27 positive. Sero- more descriptive name.2 For the sake of negativity for this HLA factor may por- simplicity, we’ll refer to the syndrome by tend a less severe version of the syndrome. the abbreviation RS. Individuals infected with HIV show in- creased incidence of developing RS.3 A microbial antigen is likely responsi- z Look for elements ble for the initial activation of RS. This is of the classic triad followed by an immune reaction involv- RS is notoriously inconsistent in its pre- ing the joints, skin, and eyes. This theory sentation. Only a third of patients will is supported by the absence of auto- develop the “classic triad”—that is: pe- antibodies, the frequent association with fast track ripheral arthritis lasting at least 1 month, HLA-B27, and the fact that patients with Only a third of (or ), and conjunctivi- advanced AIDS experience the same se- tis. Nearly half of patients will have only verity of RS symptoms, despite depressed patients will a single element of the triad.3 CD4+ function.1 develop the Patients with RS will complain of “classic triad”: generalized malaise and fever and will peripheral often describe dysuria with concomitant z Bacteria trigger syndrome urethral discharge. If is via 1 of 2 pathways arthritis, urethritis present, the patient will report reddened, The bacteria that trigger RS typically en- (or cervicitis), sensitive eyes. Pain will often originate ter the body through one of 2 pathways: and conjunctivitis from axial bones, lower extremities (in the genitourinary tract or the gastrointes- an oligoarticular asymmetrical pattern), tinal tract. swollen digits, and the heels (from enthe- • The sexual transmission pathway sopathy). involves with tra- Skin manifestations are often very no- chomatis or ticeable and include psoriasiform lesions 1 to 4 weeks prior to development of (FIGURE 3) on the palms, soles, and glans urethritis and possibly conjunctivitis. The penis. Specifically, you’ll see keratoderma arthritic component follows later. blenorrhagicum (FIGURE 4), brown and (In our patient’s case, his report of a red macules/papules with pustular or hy- sexually transmitted infection a year ear- perkeratotic features, on the palmar and lier did not appear to be the trigger for his plantar surfaces. Erythematous and scaly RS. We believe that another, subsequent, lesions resembling psoriatic plaques of- infection was to blame.)

812 vol 56, No 10 / October 2007 The Journal of Family Practice Rash and oligoarthritis

• The gastrointestinal pathway involves f ig u r e 3 an enteric pathogen, such as Psoriasiform plaque enteritidis, enterocolitica, Cam- pylobacter fetus, or Shigella flexneri that infects the host and follows the same time frame as noted earlier, though di- arrhea rather than urethritis emerges as a chief complaint.4 The post-venereal type of RS com- prises most cases in adults. Children who develop RS, however, are more likely to present with diarrhea rather than ure- thritis, leading the clinician to suspect a Skin manifestations of Reiter's syndrome include gastrointestinal infection as the etiology psoriasiform lesions. of the condition.5 for a polymerase chain reaction (PCR) test rather than a culture. If enteritis z Various forms of arthritis was the preceding infection, a stool cul- comprise the differential ture to elucidate potential pathogens is A number of conditions must be ruled warranted. out before the RS diagnosis is consid- You’ll also need to order serological ered definitive. The most likely impos- tests for antinuclear antibodies (ANAs), ters include: rheumatoid factor (RF), and HIV. As you • Gonococcal arthritis would expect, these tests will be abnor- • mal for systemic erythematosus, • rheumatoid arthritis, and HIV respective- • . ly. Though these tests are often negative In addition, an attack of gouty arthri- in RS patients, a strong association with tis, systemic lupus erythematosus, serum HIV infection does exist. fast track sickness, Behçet’s syndrome, rheumatic Keep in mind, too, that you can dif- Children who fever, Still’s disease, and HIV could also ferentiate gonococcal arthritis from RS present in a similar fashion. based on historical features, as well as develop Reiter’s The lab work, detailed below, sepa- clinical features, including migratory syndrome rates RS from the imposters. with necrotic and pustular are more likely skin lesions. Patients with gonococcal ar- to present with thritis will also have a positive gonococ- z Test blood and ; cal culture and rapid improvement with diarrhea rather check the ankles . than urethritis Although there is no specific test for If you order a biopsy, pathology is RS, several laboratory procedures are likely to find a variety of features in an essential to honing in on the diagno- RS patient, such as spongiform pustules, sis. Hematological inquiry will confirm neutrophilic infiltrate in a perivascular anemia, leukocytosis, thrombocytosis, pattern, and an epidermal hyperplasia and an elevated erythrocyte sedimen- that resembles psoriasis.3 tation rate (ESR). Though the urethral Radiographic imaging for a suspected test may not be positive for a suspected case of RS may reveal a number of signs organism, this procedure must be done that resemble psoriatic arthritis (pencil- to rule out gonococcal or chlamydial in-cup deformity, syndesmophytes, sac- infection. This can now be done on a roiliitis), but , particularly in urine specimen rather than inserting a the ankle joint region, should raise your swab into the . The urine is sent index of suspicion for RS.6 c o N T IN u e d

www.jfponline.com vol 56, No 10 / October 2007 813 ds n rou f ig u r e 4 lone 0.1% cream applied to scalp twice Keratoderma blenorrhagicum daily and genitals and armpits once daily, and acitretin 25 mg daily. We consulted photo to assess and treat his joint disease. We also consulted Oph- thalmology to assess for potential ocular manifestations. Though the patient did report a his- tory of a sexually transmitted infection, it occurred long before his visit, and we were unable to identify an infectious agent. As a result, we did not start him on any antibiotics. Patients with Reiter’s syndrome have brown and red macules/papules with pustular or hyperkeratotic We instructed the patient to return features on the palmar and plantar surfaces. in 2 weeks. Unfortunately, he was lost to follow-up. Patients with RS, though, z Tx: Antibiotics, NSAIDs, typically make a full recovery from their and steroids symptoms. Some patients, however— therapy for 3 months is in- 10% to 20%—may go on to have a dicated if a patient’s case of RS can be chronic, deforming arthritis.3 n traced back to an infection. If a Chlamyd- ia species is the offending organism, then References doxycycline or can be used7 1. Winchester R. Reiter’s syndrome. In Freedberg IM, Eisen AZ, Wolf K, Austen KF, Goldsmith LA, Katz SI. (strength of recommendation [SOR]: B). Fitzpatrick’s Dermatology in General Medicine. 6th If the infectious agent is unknown, then ed. New York, NY: McGraw-Hill; 2003:1769–1776. ciprofloxacin can offer broad-spectrum 2. James WD, Berger TG, Elston DM. Andrew’s Dis- coverage8 (SOR: B). eases of the Skin: Clinical Dermatology. 10th ed. Philadelphia, Pa: Saunders Elsevier; 2006. Though few studies have evaluated 3. Wolff K, Johnson rA, suurmond d. Fitzpatrick’s fast track the long-term effects of NSAID treat- Color Atlas and Synopsis of Clinical Dermatology. Though most ment on RS, a regular schedule of high 5th ed. New York, NY: McGraw-Hill, 2005. doses for several weeks is appropriate for 4. Colmegna I, cuchacovich r, espinoza lr. HLA- patients make a B27-associated : pathogenetic and inflammation and pain management. It’s clinical considerations. Clin Microbiol Rev 2004; full recovery, some most effective when given early in the dis- 17:348–369. ease course5 (SOR: B). 5. Schachner LA, Hansen RC. Pediatric Dermatology. may go on to 2nd ed. New York, NY: Churchill Livingstone, Inc; have a chronic, Topical can be used 1995. on mucosal and skin lesions. For refrac- 6. Gladman dd. clinical aspects of the spondyloar- deforming arthritis tory disease, immunosuppressive agents thropathies. Am J Med Sci 1998; 316:234–238. such as at 2000 mg/day9 7. Lauhio A, Leirisalo-Repo M, Lähdevirta J, Saikku P, Repo H. Double-blind, placebo-controlled study of (SOR: B) or a subcutaneous injection of three-month treatment with lymecycline in reactive at 25 mg twice weekly10 (SOR: arthritis, with special reference to Chlamydia arthri- tis. Arthritis Rheum 1991; 34:6–14. B) offer relief. 8. Yli-Kerttula t, luukkainen r, Yli-Kerttula u, et al. Effect of a three month course of ciprofloxacin on the late prognosis of reactive arthritis. Ann Rheum Our patient’s treatment included Dis 2003; 62:880–884. 9. Clegg DO, Reda DJ, Weisman MH, et al. Compari- an NSAID and corticosteroids son of sulfasalazine and placebo in the treatment Because our patient’s syndrome involved of reactive arthritis (Reiter's syndrome). A Depart- ment of Veterans Affairs Cooperative Study. Arthri- a variety of systemic manifestations, we tis Rheum 1996; 39:2021–2027. used several medications to cover all of 10. Flagg sd, Meador r, Hsia e, Kitumnuaypong t, his symptoms. We prescribed piroxicam Schumacher HR Jr. decreased pain and synovial inflammation after etanercept therapy in patients 20 mg daily, clobetasol 0.05% ointment with reactive and undifferentiated arthritis: an open- applied daily to legs and feet, triamcino- label trial. Arthritis Rheum 2005; 53:613–617.

814 vol 56, No 10 / October 2007 The Journal of Family Practice