Behçet’s Disease

General Information

  • Behçet’s disease (BD) is a chronic, relapsing, multisystemic vasculitis characterized by mucocutaneous lesions, as well as articular, vascular, ocular and central nervous system manifestations.
  • BD is most often reported in populations along the Silk Road, with highest prevalence reported in Turkey at >1/1,000, versus 1/10,000 in Japan. European cases are more often described in Mediterranean countries.

Clinical Manifestations

  • Onset most commonly occurs in adults, but pediatric cases have been reported.
  • Relapsing episodes of round oral aphthae with sharp erythematous and elevated borders (1-3 cm diameter) may be accompanied by genital aphthae (>50%); cutaneous features may include pseudo-folliculitis and erythema nodosum.
  • Ocular disorders (posterior uveitis, retinal vasculitis) occur in over 50% of BD patients.
  • Arthralgia and/or arthritis are frequent (45%) and can occur as an initial symptom.
  • Vasculitis in BD is more frequent in the venous system where thromboses in femoro-iliac, superior and inferior vena cava and cerebral territories may occur. Rarer arterial thromboses and aneurysms primarily affect the pulmonary vessels.
  • Sporadic neurological manifestations (neuro-BD) are frequent (>20%), often occuring 1-10 years after intial symptoms, and may include headache, pyramidal signs with hemiparesis, behavioral changes and sphincter dysfunction.
  • Aphthoid and/or ulcerative lesions may affect the whole digestive tract but mainly the ileo-cecum and ascending colon, potentially leading to hemorrhages and perforations.

Etiology

  • Of unknown origin, genetic predisposition in BD may allow certain infectious (in particular Streptococcus sanguis) and/or environmental insults to trigger symptoms involving sporadic inflammatory attacks reminiscent of auto-inflammatory disorders due to cross reactions with oral mucosa antigens.
  • HLAB5101 antigen is associated to BD in 50-70% of patients and aberrant cytokine levels (eg- IL-6, TNF-a, IL-8, IL-12, IL-17 and IL-21) have been implicated in the pathogenesis of BD.

Diagnosis

  • International classification criteria, as defined by clinical presentation, are sensitive and specific.
  • The presence of recurrent oral aphthae, at least 3 times over 12 months, is mandatory, in combination with two of the following:
    • Recurrent genital ulceration
    • Eye lesions
    • Skin lesions
    • Pathergy
  • In neuro-BD, lumbar puncture is mandatory and MRI may reveal inflammatory lesions in the cerebral trunk, brainstem and hemispheric areas.

Differential

  • Depending upon manifestations, infectious uveitis, relapsing polychondritis, sarcoidosis, antiphospholipid syndrome, Takayasu arteritis, Crohn disease or multiple sclerosis may be considered.

Management

  • Anti-inflammatory steroids are the basis of treatment, however, corticodependance and relapses may occur upon discontinuation.
  • Concurrent administration of immunosuppresive drugs (e.g. azathioprine, cyclophosphamide, methotrexate), are also prescribed but their action is delayed.
  • Infliximab and alpha-interferon (2a or 2b) are efficient, particularly in severe uveitis, and antiagregant or anticoagulation treatments are used in the case of vascular involvement.
  • Colchicine relieves mucocutaneous symptoms. Efficacy is dependent upon rapid initiation and patient compliance.

Prognosis

  • In the absence of treatment, the prognosis is severe due to ocular involvement leading potentially to blindness, the risk of lethal arterial rupture and neurological symptoms potentially causing encephalopathy that may lead to a loss of autonomy.
  • Intensive ophthalmological care coupled with immunosuppressive treatment has been shown to reduce morbidity greatly..

Orphanet: an online rare disease and orphan drug data base. Copyright, INSERM 1997. Available on http://www.orpha.net.Accessed (3.13.15).

Answer to CC #7

Case Challenge #7 presented a 26 year old Asian male with his 3rd episode of headache and neck stiffness associated with uveitis, oral ulcers, and genital ulcers. Labs revealed a leukocytosis and CSF with 45 cells (85% Lymphs), protein of 65, normal glucose, a negative gram stain.

We asked which of the following would be most compatible with the most likely diagnosis?

The results of the voting are as follows:

Behcet Results
The correct answer is:

Pustule at the site of a blood draw, or (Pathergy!)

This patient has Behçet’s disease, a multisystem inflammatory disease marked by:
  • Recurrent oral aphthous ulcers and at least 2 of the following:
    • Recurrent genital ulcers
    • Ocular lesions: uveitis or hypopyon
    • Pathergy (pustule at site of needle stick)
  • Ethnicity: Asian or Eastern Mediterranean descent
  • Also associated with GI disease and recurrent aseptic meningitis
  • Rx: Colchicine

As seen in our previous post, pathergy phenomenon is when a small red bump or pustule occurs 1 to 2 days after a forearm is pricked with a sterile needle. This test is often associated with Behcet’s disease having a low sensitivity but high specificity for the disease, as a positive test supports a diagnosis of Behcet’s and is not definite. This past week’s NEJM had a case of a patient with newly diagnosed Behcet’s disease and a positive pathergy test. Click on the links below to read the article from NEJM and learn more from the Hopkins Vasculitis Center.

The Johns Hopkins Vasculitis Center – Behcet’s Disease

A 25-Year Old Man with Oral Ulcers, Rash, and Odynophagia 

Thanks for playing, case challenge #8 will be posted next week!

Idiopathic Pulmonary Fibrosis

This morning, Dr. Zea Borak presented an interesting talk on idiopathic pulmonary fibrosis  at Grand Rounds. Perfect time for a quick primer on this rare condition!

General Information

Idiopathic pulmonary fibrosis (IPF) is a nonneoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known cause. IPF is a rare disease that affects approximately 5 million people worldwide. The prevalence is estimated to be slightly higher in men (1/5000) than in women (1/7700).

Clinical Manifestations 

The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathlessness and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease and classic signs of right heart failure may be present.

Etiology 

The etiology is not yet completely understood. Environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock).

Diagnosis 

IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP). The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that have been published in guidelines endorsed by several professional societies.

Differential Diagnosis 

includes other idiopathic interstitial pneumonias, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis), forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational) exposures.

Management 

Medical therapy is ineffective in the treatment of IPF. New molecular therapeutic targets have been identified and several clinical trials are investigating the efficacy of novel medications. Meanwhile, pulmonary transplantation remains a viable option for patients with IPF. However, IPF is typically progressive and leads to significant disability.

Prognosis 

The median survival is 2 to 5 years from the time of diagnosis.

Orphanet: an online rare disease and orphan drug data base. Copyright, INSERM 1997. Available on http://www.orpha.net. Accessed (3.13.15).