Maria Odete E. Hilário¹

Maria Teresa R. A. Terreri²

Glaúcia Prismich²

Claúdio Len²

Eduardo N. Kihara³

José Goldenberg⁴

Dirceu Solé¹

1 Associate Professor, Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics.

2 Postgraduate, Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics.

3 Neuroradiologist, Image Department of Hospital Israelita Albert Einstein.

4 Associate Professor, Division of Rheumatology, Department of Medicine.

Address for correspondence and reprint requests:

Dr. Maria Odete E. Hilário

Division of Allergy, Clinical Immunolgy and Rheumatology, Department of Pediatrics, UNIFESP - EPM.

Rua dos Otonis, 725

Sao Paulo, SP, Brazil

CEP 04025-002

FAX 55 - 11 - 5701590

Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics and Division of Rheumatology, Department of Medicine, São Paulo Federal University - Escola Paulista de Medicina, São Paulo, Brazil.

Abstract

The authors report the case of a 15 year-old male patient, HLA B27 positive, who presented a rare association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis, which resulted in death. A brief review of the literature is provided.

Key words: Ankylosing spondylitis, Crohn’s disease, Takayasu’s arteritis

Introduction

Ankylosing spondylitis is a chronic inflammatory disease, characterized by peripheral and axial joint impairment¹. Its prevalence in childhood is estimated in 0.01 to 0.08%¹. Extra-joint impairments include uveitis and cardiovascular lesions, such as conduction defects and aortitis². However, systemic vasculitis has not been described. Crohn's disease is characterized by granulomatous inflammation at the level of the gastrointestinal tract³. Extra-intestinal symptoms are frequently observed, including articular manifestations³. In cases in which HLA B27 antigen is present, involvement of the axial skeleton, as in the primary ankylosing spondylitis¹, is observed. Takayasu's arteritis is a vasculitis of giant cells which affects large vessels⁴ . The insidious manifestation, accompanied by non-specific complaints, such as fever, malaise and limb pain, is frequent. None of these diseases are frequent and their association is even more rare. The purpose of this paper is to report the case of a 15 year old male patient with a rare association of these three diseases. A brief review of the literature is given.

CASE REPORT

The patient, a 15 - year - old white male had experienced sporadic episodes of diarrhea until 10 years of age. At this point, he started having difficulty in walking, due to a pain in his right leg and lumbar spine. Indomethacin was prescribed, leading to partial improvement. Four months later, lumbar and right hip pain started, accompained by holocranial cephalea. At this time he sought our medical service and was found to be pale and undernourished. The articular examination revealed severe spine and right hip joint limitations, rectification of lumbar spine and an abnormal Schober test (from 15 to 18 cm). The blood tests showed hemoglobin of 7.4 g/dl (normal values range from 14 to 18 g/dl); normal leukocytes, platelets, alfa 2 globulin and gamaglobulin; erythrocyte sedimentation rate of 60 mm (normal values range from 01 to 07 mm); normal urea and creatinine; negative rheumatoid factor and antinuclear antibodies; normal complement level; and positive HLA-B27 antigen. The X-rays revealed bilateral sacro-iliitis, rectification of lumbar lordosis, fusion of second, third and fourth cervical vertebrae and severe osteoporosis. Based on the above, our preliminary diagnosis for this patient was spondyloartropathy and possible chronic inflammatory bowel disease.

A few weeks later, he started having liquid, yellow diarrhea, abdominal pain and weight loss. An X-ray of his intestinal transit revealed signs of inflammatory enteropathy with jejunum and ileum dysfunction. A subsequent biopsy of the small intestine enabled us to diagnose Crohn's disease. Treatment started with prednisone (1 mg/kg/day), indomethacin (2 mg/kg/day) and sulfasalazine (50 mg/kg/day), which was withdrawn one month later due to side-effects. The dose of prednisone was tempered to 5 mg every other day, with amelioration of the diarrhea. The patient improved and although complaining of sporadic cervical and pelvic pain, was able to perform regular activities.

Two years later, he began complaining of intermittent paresthesia and diminished strength of the left arm. The X-ray of the cervical spine evidenced massive fusion of the interapophyseal joints and loss of the normal curvature . Magnetic nuclear resonance showed dislocation of the first and second cervical vertebrae with severe compression of the spinal cord. Fixation of the cranial halo was performed, with traction and placement of a casted splint for the spinal arthrodesis. After 4 months, there was remission of the neurological signs and symptoms.

At 14 years of age, a progressive decrease of radial pulses was detected, leading to absence. During this period, transient loss of consciousness, severe headache with decreased visual acuity, and tonic-clonic convulsion (which ceased without medication) were observed. The patient presented partial mydriasis of the left pupil, diminished muscle strength of the upper limbs, and absence of carotid and upper limb pulses. An Eco Doppler exam, was performed and revealed ectasy of the ascending aorta, severe arteritis with complete carotid occlusion and filling of the left carotid by collaterals. Computerized tomography of the spine and brain showed no changes. The digital aortography showed narrowing of the discending aorta with occlusion of the supra-aortic branches and intense collateral vessels supplying the carotid and vertebral circulation, stenosis of the distal aorta with no involvement of the abdominal branches . Based on these findings, type III Takayasu's arteritis was diagnosed. Epidemiology, tuberculine reactivity and chest X-ray were negative for tuberculosis. At this time, prednisone (2 mg/kg/day) and azathioprine (2.5 mg/kg/day) were prescribed. Revascularization was not performed due to the inappropriate clinical condition of the patient.

Aged fifteen years and nine months, the patient arrived at the hospital in a state of coma and subsequently died.

DISCUSSION

We have reported the case of a 15 year old male who presented a rare association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis.

Peripheral articular manifestations of the Crohn's disease occur in parallel with the development of digestive symptoms in 15% of patients. They are characterized by asymmetric oligo- or polyarthritis, predominantly in the lower limbs. In general, the arthritis associated with Crohn's disease is not destructive. In such cases, both rheumatoid factor and HLA-B27 antigen are not present⁵. The antigen HLA-B27 is present in 70% of the cases with axial involvement, whereas in primary ankylosing spondylitis, the incidence is almost 100%⁵. Symptomatic spondylitis is 30 times more common in patients with Crohn's syndrome than in the general population, and it is considered an associated disease, rather than a complication⁵. Purrmann et al in 1988 observed 7.8% of ankylosing spondylitis in 231 patients with Crohn's disease⁶. Association of Takayasu's arteritis and Crohn's disease was first described by Soloway et al in 1970, and since then few cases have been reported^{7,8,9,10,11,12,13,14,15}. According to Yassinger in 1976, the chance for this association is of one in one trillion¹⁶. Extra-intestinal manifestations, such as arteritis, erythema nodosum, pyoderma gangrenosum, and iritis, are often described as being associated with this intestinal disease. Occasional vascular complications are reported, and the involvement of large vessels are reported in children^16,17 Vasculitis may precede or succeed Crohn's disease. Although the etiology of both diseases is unknown, it is believed that they have a common pathophysiology, since both diseases present immunological alterations^18,19.

The association of Takayasu’s arteritis and tuberculosis has been controversial. Whereas some authors report different forms of tuberculosis associated with the arteritis, others like us have not found such association^20,21,22.

Ankylosing spondylitis associated with the syndrome of aortic arch (Takayasu's arteritis) was reported by Paloheimo et al²³ and also observed by other authors^24,25,26. An association of ankylosing spondylitis with Takayasu's arteritis in an HLA B27 positive patient was described by Magaro et al in 1988²⁷. Articular manifestations of Takayasu's arteritis occur in 20-50% of the cases and essentially consist of arthralgia and peripheral arthritis^26,27.

Association of the three diseases (Takayasu's arteritis, Crohn's disease and ankylosing spondylitis) was described in two adult patients out of a total of 32 patients with Takayasu's disease studied by Hall et al in 1985²². Searching the literature, we could not find a report describing the association of these three diseases in children and this encouraged us to publish this case.

Although we do not know which of the three diseases started first, we have some hypothesis. In Brazil, there is a high incidence of sporadic diarrhea associated to environmental enteropathy, particularly in low income population. The first symptom presented by our patient was diarrhea and he came from a low income family. Probably, the onset of Crohn’s disease in this patient was misdiagnosed. When the articular manifestations started, the small intestine was investigated and the diagnosis of Crohn’s disease was confirmed (biopsy). From our point of view, Crohn’s disease existed prior to the development of the articular manifestations and the diagnosis was delayed by the above mentioned facts. In addition, anti-inflammatory therapy can trigger gastrointestinal manifestations . In this case, it is not possible to estimate the extent to which this therapy activated the event.

It is difficult to suggest a common pathophysiology or a genetic marker for these three diseases. There is no argument wich substantiates the relationship among them. Otherwise there is a possibility of the casual occurrence. More evidence in the literature is necessary to allow us to understand such association.

Acknowledgement:

To Marina R. Quaresma, MD, for the english revue and the precious suggestions.

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