| Abstract|| |
Background: Reactive arthritis (ReA) is defined as a peripheral arthritis lasting longer than 1 month, associated with urethritis, cervicitis, or diarrhea. The reported annual incidence of ReA is approximately 30-40 cases per 100,000 adults, occurring commonly in the age group of 16 and 35 years. It is known to be associated with gastrointestinal infections with Shigella, Salmonella, and Campylobacter species and other microorganisms, as well as with genitourinary infections (especially with Chlamydia trachomatis). Case Report: This article reports the case of a 53-year-old, post-right total hip replacement, Indian man, with ReA, who presented with fever, respiratory distress, and abdominal discomfort. He complained of itching, tingling sensation, pain on urination, and retention of urine. He had right hip joint pain for 3 weeks, inability to move right leg since 10 days, and melena since 1 week. Laboratory tests revealed anemia, high liver and kidney function tests, elevated erythrocyte sedimentation rate, C reactive protein, procalcitonin and occult blood in stool. He tested positive for hepatitis C virus genotype 3. Gastroduodenoscopy revealed multiple apthoid ulcers at D2 and large gastric varix. Ultrasonography of whole abdomen revealed cholelithiasis and splenomegaly. Skin lesions and arthritis led to the diagnosis of associated ReA. The patient was managed conservatively and discharged in a stable condition. Conclusions: Our case is unlike classical ReA because the patient is older, HLA B27 negative, and without florid urethritis. Admitted for fever and lower urinary tract symptoms, along with respiratory distress, the primary objective of the emergency doctors was to prevent the patient from progressing to organ failure. The diagnosis of underlying atypical/incomplete ReA could easily have been missed without adequate awareness, dermatological consultation, and a skin biopsy.
Keywords: Hepatitis C virus genotype 3, reactive arthritis, Reiter′s syndrome
|How to cite this article:|
Lodh M, Ahmed MA, Niyogi BG, Bandyopadhyay B. Portal hypertension and an atypical reactive arthritis like presentation in a patient infected with hepatitis C virus genotype 3. Indian J Dermatol 2014;59:584-7
|How to cite this URL:|
Lodh M, Ahmed MA, Niyogi BG, Bandyopadhyay B. Portal hypertension and an atypical reactive arthritis like presentation in a patient infected with hepatitis C virus genotype 3. Indian J Dermatol [serial online] 2014 [cited 2021 Sep 28];59:584-7. Available from: https://www.e-ijd.org/text.asp?2014/59/6/584/143524
What was known?
1. Reactive arthritis (ReA) is a rare autoimmune condition that develops in response to an infection.
2. Classical ReA is seen between 16 and 35 years, the typical features being urethritis, conjunctivitis, and arthritis.
3. ReA is commonly associated with gastrointestinal (GI) infections with Shigella, Salmonella, and Campylobacter, and genitourinary infection with Chlamydia trachomatis.
| Introduction|| |
In 1916, Hans Reiter described the triad of nongonococcal urethritis, conjunctivitis, and arthritis in a young German officer with bloody dysentery. Reiter was responsible for involuntary sterilization, euthanasia, and medical experiments that killed thousands of concentration camp prisoners. This unethical practice outraged many people who strongly recommended that this syndrome should be called "ReA." 
ReA has been associated with GI and genitourinary infections. However, we present the case of a 53-year-old man, admitted to emergency department with fever, respiratory distress, abdominal discomfort, and retention of urine. He complained of itching, tingling, and painful urination. Although the acute symptoms were taken care of at the outset, the mucocutaneous changes led to a dermatological referral. Finally, the case was diagnosed as incomplete ReA. Combined handling of the case, with a multidisciplinary approach, helped quick diagnosis and effective treatment.
| Case Report|| |
A 53-year-old patient, an old case of post-right total hip replacement 18 years back, was treated with analgesics for pain in the right hip joint 3 weeks ago and developed melena which lasted about a week, followed by a period of constipation. He presented to the emergency with respiratory distress, abdominal discomfort, uneasiness, and burning sensation of body. Our patient also complained of itching, tingling, pain on urination, and retention of urine. Arterial blood gas analysis revealed metabolic acidosis, respiratory alkalosis, hypoxia, hyponatremia (sodium 119 mmol/L), and anemia. On admission, he had low-grade fever, pallor, tachypnea, and tachycardia. The patient also had a history of upper GI bleed.
On examination, the patient was found to be obese and pale. Diffuse coarse crepitations were auscultated all over his chest, there was free fluid in his abdomen and there were clots around his anus. He was not able to flex his right hip or move his right leg since the last 10 days. There was tenderness in right hip joint. He complained of pain in hip joints since the last 3 weeks. Computed tomography scan of pelvis revealed post-right hip replacement intact prosthesis in situ and arthritic changes in left hip joint. The patient was transfused two units of blood of AB+ group. Electrocardiogram (ECG) revealed sinus tachycardia, and ultrasonography (USG) screening of abdomen revealed dilated bowel loops. There were 5-9 calculi in the gall bladder and splenic span measured 14.9 cm.
Laboratory investigations revealed the following results (reference ranges in parentheses). Hemoglobin 4.3 g/dL (13-17 g/dL), platelet count 2.64 lakhs/cumm (1.5-4 lakhs/cumm), white blood cells count 17,400 (4000-10,000/cumm), and erythrocyte sedimentation rate (ESR) 135 mm 1 st h (5-15 mm 1 st h). Lactate levels were 11 mg/dL (4.5-19.8 mg/dL). Procalcitonin levels of 1.10 ng/mL (<0.5 ng/mL) indicated systemic infection. D dimer was high at 862.91 ng/mL (<500 ng/mL) and prothrombin time and fibrinogen were within reference ranges. Stool was positive for occult blood. Bilirubin levels were 1.3 mg/dL (upto 1 mg/dL), alanine transaminase 144 U/L (0-35 U/L), aspartate transaminase 229 U/L (0-35 U/L), and albumin 2.8 g/dL (3.5-5 g/dL). Alkaline phosphatase and gamma glutamyl transferase were within the reference range. Serum urea levels were also high at 154 mg/dL (15-40 mg/dL) and creatinine was 1.8 mg/dL (0-1.5 mg/dL).Human leukocyte antigen B 27 (HLA-B27) antigen was negative. C reactive protein was 41.21 mg/L (upto 6 mg/L) and serology for hepatitis C virus was reactive by immunochromatography and enzyme linked immune sorbent assay. Hepatitis C virus (HCV) RNA quantification by real-time polymerase chain reaction (PCR) revealed a result of 1.28 × 107 IU/L. HCV was of genotype 3. Blood and urine culture were negative for any organism. Gastroduodenoscopy revealed multiple apthoid ulcers at D2 and large gastric varix for which injection glue was given.
There were erythematous elevated skin lesions around umbilicus [Figure 1], palm [Figure 2], and around the eyes [Figure 3]. Skin biopsy revealed irregular acanthosis, hyperkeratosis, parakeratosis, and neutrophillic exocytosis of the overlying squamous epithelium [Figure 4]. The parakeratotic layer showed neutrophillic collections. The dermis showed mild perivascular chronic inflammatory cell infiltrate [Figure 5]. The arthritis was asymmetrical, polyarticular, and mainly involved the joints of the lower extremities. The patient also complained of pain in bilateral wrist joints, for which orthopedic opinion was taken and a diagnosis of ReA was made.
|Figure 4: Acanthosis, hyperkeratosis, and parakeratosis of the epidermis|
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|Figure 5: Parakeratotic layer with neutrophillic cells and dermis with chronic inflammatory cells|
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For hepatitis C, the patient was started on injection alpha interferon and oral ribavirin, and after 12 weeks of treatment, the HCV RNA fell to <250 IU/mL. Then ribavirin was put on hold because of low hemoglobin levels.
| Discussion|| |
ReA has been classified into HLA-B27-associated and nonassociated forms, and a number of other clinical features associated with ReA have been observed. According to the American Rheumatism Association criteria, patients with ReA generally have asymmetric polyarthritis that lasts at least 1 month, as well as 1 or more of the following features: Urethritis, inflammatory eye disease, mouth ulcers, balanitis, or radiographic evidence of sacroilitis, periostitis, or heel spurs. Prolonged intracellular bacterial survival promoted by B27, other factors, or both permit trafficking of infected leukocytes from the site of primary infection to joints, where a T-cell response to persistent bacterial antigens may then promote arthritis.
The reported annual incidence of ReA is approximately 30-40 cases per 100,000 adults, with a prevalence of 1-7%, but this varies greatly among different geographic locations.  Reports from Latin America, North Africa, India, and Thailand showed low prevalence, with minimal differences between countries.  Majority of ReA have been reported to occur between the ages of 16 and 35 years.  Diarrhea precedes the onset of ReA in 80% of the cases, unlike that in adults where diarrhea is not a prominent feature.  Most cases of ReA usually follow an infection (1-3 weeks later).  The classic triad of arthritis, urethritis, and conjunctivitis was not present in this patient. Eye involvement may be absent or subclinical in ReA.  Skin findings in classic ReA are keratoderma blennorrhagica (thick yellow pustular scaly lesions on the plantar aspect of feet) and balanitis circinata (psoriatic plaques on penis). Psoriatic plaques may be present in 5% cases over extensor surface of legs, hands, nails, scalp, and fingers. Microabscesses are seen. In this patient, scaly periumbilical lesions, and scaly psoriasiform lesions on palm and on eyelids were the dermatological findings. Skin biopsy in our case showed parakeratosis and acanthosis. Around 62% of patients with ReA and ankylosing spondylitis, regardless of HLA B27 phenotype or GI symptoms, have evidence of ileitis, ileocolitis, or colitis on histopathology. 
The elevated ESR, neutrophillic leukocytosis, elevated C reactive protein, and procalcitonin levels all suggested an infection. No organism was isolated from blood or urine. Elevated ESR and acute phase reactants are usually found in cases of ReA. Anemia was probably related to GI bleed. The negative report obtained for urine, stool, and urethral swab cultures in the patient does not negate a diagnosis of ReA. Long-term follow-up studies suggest that some joint symptoms persist in 30-60% of patients with ReA. Recurrences of the acute syndrome are common, and as many as 25% cases evolve into chronic illness leading to disability which may make the patient unable to work or force to change occupation.  Cardiac signs such as aortic regurgitation, central or peripheral nervous system lesions, and pleuropulmonary infiltrates are rare manifestations of RA. 
Only 30-50% of ReA patients are HLA-B27 positive, and recent data suggest this haplotype might predispose more to disease severity rather than disease susceptibility.  HLA-B27 positivity is associated more with chronic or relapsing arthritis, uveitis, aortitis, sacroilitis, and spondylitis. , Our patient was HLA-B27 negative. Olivieri et al. described a RA-like polyarthritis and a less common mono-oligoarthritis involving medium sized and large joints, often showing an intermittent course, in HCV patients. This latter form is associated with the presence of serum cryoglobulins.  No documentation could be found of RA in HCV cases.
The arthritis in our patient was asymmetrical and polyarticular, involving mainly the lower extremity joints. Rathod et al.  have even described symmetrical, mutilating polyarthritis with typical skin lesions of multiple well-defined, irregular, erythematous, hyperkeratotic, scaly, and itchy plaques all over the body including lips, not easily distinguishable from pustular psoriasis.
The advent of PCR analysis has added much insight and clarity into the pathophysiology of ReA. The debate continues, however, whether these ReA patients experience a disseminated persistent infection that is the driving force of their ReA, or if the disseminated presence of these causative organisms simply lays the foundation for an autoimmune phenomenon through a mechanism that is not completely understood.  Paralleling the opposing schools of thought regarding the pathophysiology of the disease, both traditional disease-modifying antirheumatic drugs and antibiotics have been assessed as potential therapeutic options.
| Conclusion|| |
Our case is unlike classical ReA because the patient is older, HLA-B27 negative, and without florid urethritis. This topic should be more accurately studied in the future to exclude a spurious association between the two events.
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What is new?
1. Authors strongly recommend skin biopsy when atypical presentations of RA are seen as in our case having scaly periumbilical lesions, and scaly psoriasiform lesions on both palms and eyelids. It could be very important in confirming your suspicion.
2. The patient may be HLA-B27 negative and without florid urethritis. Associated HCV infection may exist.
3. HLA-B27-negative patient with reactive arthritis is likely to have a better prognosis, as in our case.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]