Skip to main content
Open Access Publications from the University of California

Dermatology Online Journal

Dermatology Online Journal bannerUC Davis

Clinical tetrad of arthritis, urethritis, conjunctivitis, and mucocutaneous lesions (HLA-B27-associated spondyloarthropathy, Reiter syndrome): Report of a case

Main Content

Clinical tetrad of arthritis, urethritis, conjunctivitis, and mucocutaneous lesions (HLA-B27-associated spondyloarthropathy, Reiter syndrome): Report of a case
K Chudomirova MD PhD, Ts Abadjieva MD, R Yankova MD PhD
Dermatology Online Journal 14 (12): 4

Department of Dermatology and Venereology, Medical University, Plovdiv, Bulgaria.


A 21-year-old male patient with the clinical tetrad of arthritis, urethritis, conjunctivitis, and mucocutaneous lesions, commonly known as Reiter syndrome was presented. He was hospitalized in poor condition, with fever, bilateral conjunctivitis, swollen and painful knee and tarsal joints, low back pain, Achilles tendonitis, dactilitis, keratoderma blenorrhagica, purulent urethritis, circinate balanitis, and oral erosive lesions. Radiography and Computerized Axial Tomography (CAT) showed sacroileitis, spondilosis thoracalis, and arthritis of the feet. The laboratory studies revealed anemia, neutrophilic leukocytosis, elevated erythrocyte sedimentation rate (ESR), hypoalbuminemia, negative rheumatoid factor, pyuria, proteinuria, and the presence of HLA-B27. The microbiological examinations of samples from pustular lesions, throat, eyes, urethra, stool, and blood were sterile. Urethral smear was positive for Chlamydia trachomatis (PCR). The histopathological picture of skin lesions was consistent with pustular psoriasis. Systemic treatment with antibiotics, corticosteroids, and non-steroidal anti-inflammatory drugs produced clinical improvement. This clinical syndrome requires comprehensive evaluation and multidisciplinary management.


The clinical syndrome of arthritis, urethritis, conjunctivitis, and mucocutaneous lesions, commonly known as Reiter syndrome, is a multisystem disorder triggered by genitourinary or enteric infection. It is defined by the American Rheumatism Association criteria subcommittee as one month of peripheral arthritis associated with urethritis, cervicitis, or both. The syndrome is more common as the sexually acquired reactive arthritis (SARA) (endemic) form than the enteric (epidemic) form. The classic triad of the disease, namely urethritis, arthritis, and conjunctivitis presents in only one-third of patients, and the tetrad, with the addition of the mucocutaneous findings of balanitis and keratoderma blennorrhagica is described very rarely [1, 2].

Clinical synopsis

Figure 1Figure 2
Figure 1. Keratoderma blenorrhagica (feet)
Figure 2. Keratoderma benorrhagica (hands)

The onset of the disease of a 21-year-old male patient manifested with skin rash, pain, and swelling of the joints. The treatment with systemic antibiotics and local antiseptics was ineffective; two months later the patient was hospitalized at the Department of Dermatology and Venereology, University Hospital in Plovdiv, in severe condition. His clinical signs and symptoms malaise, fever, and myalgia. The clinical examination revealed bilateral conjunctivitis, swollen and painful knee and tarsal joints, low back pain, enthesopathy, Achilles tendonitis, and dactilitis. Pustules and psoriasiform hyperkeratotic skin papules and plaques on the palms and soles (keratoderma blenorrhagica), erythemosquamous plaques on the scalp, nail changes (subungual hyperkeratosis, thickening of the nail plate and onycholysis), and erythematous plaques and erosions on the tongue and bucal mucosa were noted. Purulent urethritis accompanied by circinate balanitis was also present (Figs. 1-4). The chest X-ray showed interstitial pulmonary infiltrates and the abdominal sonography revealed hepatosplenomegaly. Electrocardiograpgy and echocardiography were normal.

Figure 3Figure 4
Figure 3. Oral mucousal lesions
Figure 4. Circinate balanitis

The laboratory studies revealed anemia (hemoglobin 10.6g/dl), leukocytosis (leukocytes 18K/mm3, neutrophilia (neutrophils 78%), lymphopenia (lymphocytes 13%), elevated ESR (102 mm/h), elevated liver enzymes (AST 180 U/l, ALT 78 U/l), fibrinogen (6.3g/l), C-reactive protein (CRP) (159 mg/l), hypoalbuminemia (albumin 3.1g/dl), negative rheumatoid factor, and negative antinuclear antibodies (ANA). The urinalysis showed leukocytes, erythrocytes, and protein. The microbiological cultures of secretions from pustular skin, throat, eyes, and blood were sterile. The microscopic examination of the urethral smear noted more than 20 polymorphonuclear leucocytes (PMNL) per high power field (hpf). The urethral smear was positive for Chlamydia trachomatis (PCR) and negative for Neisseria gonorrhoeae (PCR, culture), Mycoplasma spp., and Candida spp. (culture). Stool was negative for Salmonella spp, Shigella spp. and Yersinia spp. (culture). Serological tests for C. trachomatis (IgA/IgM/IgG EIA), C. pneumoniae and M. pneumoniae (EIA), syphilis (VDRL, TPHA), Lyme disease (EIA), HIV, hepatitis B and C virus were negative. HLA-B27 antigen positivity was detected. Imaging studies (radiography and CAT) noted features of sacroileitis, spondilosis thoracalis incipiens, and arthritis of the feet. The histopathological picture of the skin lesions was consistent with pustular psoriasis - subcorneal spongiform pustules, psoriasiform epidermal hyperplasia, and a perivascular neutrophilic infiltrate in the superficial dermis (Figs. 5 & 6).

Figure 5Figure 6
Figure 5. Histopathological findings: subcorneal spongiform pustules (H&E)
Figure 6. Histopathological findings: psoriasiform epidermal hyperplasia, perivascular neutrophilic infiltrate in the superficial dermis (H&E)

A one-month systemic treatment with antibiotics, (azithromycin, clindamycin), corticosteroids (methylprednisolone 80mg/I.m. initial dose with taper), and non-steroid anti-inflammatory drugs (NSAIDs) (meloxicam) produced improvement of the clinical status and the laboratory parameters. We used corticosteroids to reduce the severe inflammation; we did not start with methotrexate because of the anemia and elevated liver function tests. For personal reasons the patient left the hospital, but was given advice to continue the treatment with NSAIDs and emolients. We have no information about the ongoing course of his disease.


The clinical syndrome of arthritis, urethritis, conjunctivitis, and mucocutaneous lesions is recognized as a diagnostic set of clinical manifestations. Diagnosis is often complicated by the clinical polymorphism and multisystem involvement of the disease.

Urethritis with sterile pyuria and mucopurulent secretion is usually an early manifestation, described in 56-61 percent of patients [1, 3]. Circinate balanitis is the most common skin feature in 36 percent [1, 4]. Stomatitis and mucosal ulcerations on the tongue, bucal mucosa, and palate are reported in as many as 17 percent of cases [3] and keratoderma blennorrhagica is described in 15 percent [5]. Nail involvement is noted in 20-30 percent [6]. Arthritis and enthesopathia, usually involving the plantar fascia and Achilles tendon, are characteristic features; dactylitis ("sausage digits"), spondylosis, and sacroileitis are described in 31-50 percent [1, 7]. Eye changes (conjunctivits, uveitis, iritis, iridocyclitis, and impaired vision) are noted in 22-56 percent of the patients with the sexually acquired form [1, 3, 8]. Two or tree main signs were present in 15-42 percent of the patients studied [1, 3], whereas all four disease signs were found in 15 percent [1].

Reactive arthritis may be associated with other systemic symptoms. The most common heart complications are due to granulomatous lesions at the aortic root and arch that cause abnormalities in conduction, complete heart block and aortic regurgitation. Nephropathy characterized by proteinuria [1, 9] and pulmonary infiltrates (as in our patient) have been described as rare [10]. The hepatosplenomegaly and elevated liver enzymes found in our case might also be part of this syndrome. The values of the liver enzymes became normal on discharge from hospital.

This syndrome is considered to be a genetically determined host response to a specific antecedent genitourinary (C. trachomatis, Ureaplasma urealyticum) or enteric (Shigella, Salmonella, Yersinia, Clostridium and Campylobacter organisms) infection. Chlamydia-induced arthritis is the most frequent form of reactive arthritis - in 63 percent of the urogenic reactive arthritis [11]. In our case a PCR positive urethral sample for C. trachomatis was found. The suggestion that the organisms are not only triggering factors and that the urogenital form is associated with the presence of the infective agent in the affected joint is based on numerous studies showing C. trachomatis in the inflamed joint (in synovial fluid and tissue) by using molecular methods [3, 12, 13].

HLA-B27 haplotype, one of the factors contributing to the disease development, increases the risk and is found in 70-80 percent of patients with reactive arthritis [1, 14]. HLA-B27 probably shares some molecular characteristics with bacterial epitopes; an autoimmune cross-reaction is believed to take part in the pathogenesis [15].

The differential diagnosis in our case included a septic condition, septic arthritis, infectious arthritis, gonococcal arthritis, rheumatoid and psoriatic arthritis, subcorneal pustulosis, acute exanthematic pustulosis, ankylosing arthritis, Behcet syndrome, Lyme disease, and gout. The combination of arthritis, conjunctivitis, urethritis and mucocutaneous lesions lead to our diagnosis.

Reactive arthritis is a therapeutic challenge. The administration of antibacterials may be useful in uroarthritis [16]. Non-steroid anti-inflammatory drugs and sulfasalazine are still the drugs most commonly used in the treatment. Steroids are administered when inflammatory symptoms are resistant to NSAIDs [17]. Experiences with other disease modifying antirheumatic drugs such asazathioprine, methotrexate, and cyclosporin can be employed in patients who are unresponsive to the more usual medicaments. In more aggressive cases, TNF-alpha blockers could represent an effective choice [18]. Our case showed a good response to antibiotics, corticosteroids, and NSAIDs, but left the hospital and was lost to follow up.

None of the tests or the clinical signs alone are enough to make a definite diagnosis and there is no gold standard. The offending organism may not be recoverable by the time the symptoms appear. Evaluation of the combination of clinical presentation and laboratory parameters is necessary to make the diagnosis. The disease often has an unfavorable outcome, with recurrences and persistent symptoms. It requires comprehensive evaluation and multidisciplinary management. Early recognition and appropriate treatment can help to limit disability.


1. Pavlica L, Mitrovic D, Mladenovic V, Popovic M, Krstic S, Andelkovic Z. Reiter's syndrome-analysis of 187 patients. Vojnosanit Pregl 1997;54:437-46. PubMed

2. Schneider JM, Matthews JH, Graham BS. Reiter's syndrome. Cutis 2003;71:198-200. PubMed

3. Doroshenko IuA, Nikonova EN. Reactive arthritis: current characteristics and the role of Chlamydia infections in development of a clinical picture. Ter Arkh 2001;73:40-3. PubMed

4. Keat A. Reactive arthritis. Adv Exp Med Biol 1999;455:201-6. PubMed

5. Calin A. Keratoderma blenorhagicum and mucocutaneous manifestations of Reiter's syndrome. Ann Rheum Dis 1979;38:68-72. PubMed

6. Coskun BK, Saral Y, Ozturk P, Conskun N. Reiter syndrome accompanied by Terry nail. JEADV 2005;19:87-9. PubMed

7. Parker CT, Thomas D. Reiter's syndrome and reactive arthritis. J Am Osteopath Assoc 2000;100:101-4. PubMed

8. Kiss S, Letko E, Qamruddin S, Baltatzis S, Foster CS. Long-term progression, prognosis, and treatment of patients with recurrent ocular manifestations of Reiter's syndrome. Ophthalmology 2003;110:1764-9. PubMed

9. Omdal R, Husby G. Renal affection in patients with ankylosing spondylitis and psoriatric arthritis. Clin Rheumatol 1987;6:74.PubMed

10. Thiers H, Pinet. [Reiter's syndrome with inclusion body urethritis, labile pulmonary infiltration and keratoderma]. Lyon Med 1950;183:51.PubMed

11. Fendler C, Laitko S, Sorensen H, Gripenberg-Lerche C, Groh A, Uksila J, Granfors K, Braun J, Sieper J. Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis. Ann Rheum Dis 2001;60:337-43. PubMed

12. Taylor-Robinson D, Gilroy CB, Thomas BJ, Keat AC. Detection of Chlamydia trachomatis DNA in joints of reactive arthritis patients by polymerase chain reaction. Lancet 1992;340:81-2. PubMed

13. Zeidler H, Kuipers J, Kohler L. Chlamydia-induced arthritis. Curr Opin Rheumatol 2004;16:380-92.PubMed

14. Brewerton DA, Caffrey M, Nicholls A, Walters D, Oates JK, James DC. Reiter's disease and HLA-27. Lancet 1973;2(7836):996-8.PubMed

15. Eapen BR. A new insight into the pathogenesis of Reiter's syndrome using informatic tools. Int J Dermatol 2003;42:242-3. PubMed

16. Lauhio A, Leirisalo-Repo M, Lahdevirta J, Saikku P, Repo H. Double-blind, placebo-controlled study of three-month treatment with lymecycline in reactive arthritis, with special reference to Chlamydia arthritis. Arthritis Rheum 1991;34:6-14. PubMed

17. Palazzi C, Olivieri I, D'Amico E, Pennese E, Petricca A. Management of reactive arthritis. Expert Opin Pharmacother 2004;5:61-70. PubMed

18. Oili KS, Niinisalo H, Korpilahde T, Virolainen J. Treatment of reactive arthritis with infliximab. Scand J Rheumatol 2003;32:122-4.PubMed

© 2008 Dermatology Online Journal