Behcet’s Disease

Mark Stillwell, MD, FACP

 Behcet’s Disease- Introduction
• Behcet’s Disease- Introduction.......an autoimmune vasculitis associated
with *recurrent mucosal ulcers, skin lesions, uveitis, arthritis, chronic
aseptic meningitis, and other systemic manifestations. The *classic triad is
of recurrent oral ulcers, genital ulcers and uveitis.
• I. Immune Activation and Dysfunction
• A. Molecular mimicry/bacterial response- possible pathogenic role of
certain bacterial antigens that have cross-reactivity with human
peptides......specifically Behcet’s patients tend to have elevated levels of
antibodies to epitopes of mycobacterial heat shock proteins, some of which
have significant homology to human heat shock proteins.
• B. Patients may have a hyperactive response to Streptococcal antigens,
some species may precipitate attacks and many have increased Strep
antibody levels.
 Behcet’s Disease- Introduction
• Behcet’s Disease- Introduction
• I. Immune Activation and Dysfunction
• C. Altered innate immune function- patients have low levels of
mannose-binding lectin, which activates the complement cascade after
binding to carbohydrates on micro-organisms.
• D. Cellular immunity- autoreactive T cell production of cytokines (Il-2, Il-
6, Il-8, Il-12, Il-18, TNF-alpha and interferon gamma) play a role in
pathogenesis.
• E. Autoantibodies with immune compex formation play a role..... against
mucosal antigens, endothelial cells, T cell costimulatory molecule CTLA-4,
killer immunoglobulin-like receptors, LDL and kinectin.
• F. Endothelial cell activation leading to vascular inflammation and
altered coagulation.
• G. Neutrophil activation.
 Behcet’s Disease- Introduction
• Behcet’s Disease- Introduction
• II. Histopath
• A. Necrotizing, leukocytoclastic vasculitis and venous thrombosis
with lymphocytic infiltration of capillaries, veins and arteries of all
sizes. Neutrophils and CD4+ cells are found around the vasa vasorum
and perivascular areas. There is consequent endothelial swelling,
extravasation of RBCs, fibrinoid necrosis of blood vessel walls and
often there is thrombosis present.
 Behcet’s Disease- Epidemiology
• Behcet’s Disease- Epidemiology
• I. Highest prevalence and disease severity is seen in populations
along the “silk road route” in the Middle- and Far-East with similar
prevalence in men and women in those regions. Highest incidence
occurs in Turkey
• A. In the US and in Northern Europe, it is actually more common in
women, but severity worse in men, and tends to develop in young
adults 20-40 yo.
• B. Those with certain HLA types have increased risk, especially HLA-
B51.......therefore it appears that genetic composition may play a role
in disease susceptibility.
 Behcet’s Disease- Clinical
• Behcet’s Disease- Clinical......greatest morbidity and mortality occur with
ocular disease (2/3 of patients), vascular disease (1/3 of patients) and CNS
disease (10-20% of patients). Cutaneous, mucosal and articular
manifestations are common.
• I. **Oral ulcerations- most patients have *recurrent oral aphthous
ulcerations (i.e. canker sores)....often painful and multiple, round, few mm-
2 cm diameter, with well-defined borders, white-yellow necrotic base and
often surrounding erythema. Healing of a particular ulcer occurs in 1-3
weeks. As they can occur in crops, some patients have ulcers at all times.
• II. **Urogenital ulcerations- 75% of patients have these lesions, which are
**the most specific lesion for Behcet’s disease. Recurrence is less frequent
than in oral ulcerations. Lesions appear similar to oral aphthous ulcers, and
occur on the vulva (sometimes labia, vagina or cervix too), scrotum and
around the anus. Occasionally they can cause epididymitis, salpingitis or
urethritis.
Behcet’s lesions
Source: slideshare.net
Behcet’s lesions
Source: slideshare.net
Behcet’s lesions
Source: grepmed.com
 Behcet’s Disease- Clinical
• Behcet’s Disease- Clinical
• III. *Cutaneous lesions- occur in over 75% of patients.
• A. Acneiform lesions and papulopustular eruptions- more common in those
patients with arthritis. Lesions are popular and pustular, and appear similar to acne.
They often are not sterile, containing Staph aureus and Prevotella.
• B. “Pathergy”- papule or pustule developing within 48 hours of trauma or
scratch.
• C. Pyoderma gangrenosum
• D. Erythema nodosum with panniculitis/medium vessel vasculitis
• E. Erythema multiforme
• F. Pseudofolliculitis (razor bumps)
• G. Superficial thrombophlebitis
• H. Enlarged capillaries around nailfolds
Behcet’s lesions
Source: slideshare.net
Pyoderma gangrenosum in Behcet’s
Source: researchgate.net
 Behcet’s Disease- Clinical
• Behcet’s Disease- Clinical
• IV. **Ocular disease- occurs in 25-75% of patients, commonly
progresses to blindness if untreated, less severe in North American
populations.....higher risk and with more severe disease in males.
• A. **Uveitis is often the dominant feature of Behcet’s disease,
typically bilateral and episodic, with 20% having an associated
hypopyon with purulent material.
• B. May have retinal vasculitis, vascular occlusion, optic neuritis,
neovascularization, cataracts, glaucoma or macular edema.
• V. Arthritis- nonerosive, asymmetric, often intermittent and non-
deforming in 50% of Behcet’s patients.....often involving larger joints
such as knee, ankle or wrist.
 Behcet’s Disease- Clinical
• Behcet’s Disease- Clinical
• V. Neurologic- occurs in < 10%
• A. Non-parenchymal- acute or chronic, aseptic meningitis, cerebral
venous or dural sinus thrombosis, intracranial hypertension syndrome
(pseudotumor cerebri), arterial thrombosis/CVA, dissection or
aneurysm.
• B. Parenchymal- often multifocal and can involve cerebrum,
brainstem, cerebellum or spinal cord.....and lesions can be seen on
MRI, with an appearance/presentation similar to MS.
• VI. Vascular- *unlike most other vasculitic diseases, this may blood
vessels of all sizes (small, medium, large) and *can affect veins or
arteries.....leading to hemorrhage, thrombosis, aneurysm or stenosis.
 Behcet’s Disease- Clinical
• Behcet’s Disease- Clinical
• VII. GI disease- can be difficult to differentiate from inflammatory
bowel disease (IBD). Oral ulcers of Behcet’s and IBD are
indistinguishable.
• A. Discrete ulcerations can be found throughout the GI tract, but
are most common in the terminal ileum, cecum and ascending colon.
• B. Symptoms include abdominal pain, diarrhea, perforation and GI
bleeding.
• VIII. Renal, cardiac and pulmonary involvement is uncommon.
• IX. Pregnancy- carries 3x risk for flares if Behcet’s. 16% have
pregnancy complications.
 Behcet’s Disease- Diagnosis
• Behcet’s Disease- Diagnosis
• I. **Clinical scenario plus a positive **Pathergy test (skin prick test
followed by skin inflammation and ulceration causing > 2 mm papule
in 48 hours) done on flexor forearm or lip.
• II. Usually ESR/CRP are elevated during flares, WBC may be elevated,
CH50 may be elevated, often HLA-B51 positive.......only the minority of
patients are ANCA, dsDNA, RF or ANA positive, and the minority (10%)
have low C3 or C4
Pathergy (positive skin test 48 hours after needle prick)
Source:online.epocrates.com
 Behcet’s Disease- Treatment
• Behcet’s Disease- Treatment
• I. Oral/Genital ulcers
• A. Topical steroids (0.1% topical Triamcinolone cream = Orabase, 3-4x/day).
• B. Topical Sucralfate (Magic mouthwash, prepared combined with liquid antacid
and Diphenhydramine).
• C. For prevention- Colchicine 0.6 mg 2-3x/day po.
• D. Refractory lesions-
• 1. Prednisone.....if fails then:
• a. Azathioprine or Cyclosporine
• b. TNF-alpha inhibitors- Infliximab, Adalimumab, Etanercept
• c. Thalidomide
• d. Interferon alfa-2a
 Behcet’s Disease- Treatment
• Behcet’s Disease- Treatment
• II. Cutaneous lesions
• A. Erythema nodosum- Colchicine, Prednisone or Azathioprine
• B. Pyoderma gangrenosum- Prednisone, Cyclosporine,
Azathioprine or Infliximab
• III. Arthritis
• A. Colchicine
• B. Prednisone
• C. Azathioprine or Methotrexate
 Behcet’s Disease- Treatment
• Behcet’s Disease- Treatment
• IV. Ocular
• A. Topical steroids plus dilating agents
• B. Prednisone
• C. Azathioprine or Cyclosporine
• D. Infliximab or Adalimumab
• E. Cyclophosphamide
• V. GI
• A. Prednisone + Azathioprine, Sulfsalazine
• B. Refractory cases- TNF-alpha inhibitors or Methotrexate
 Behcet’s Disease- Differential Diagnosis
• Behcet’s Disease- *Differential Diagnosis
• I. HSV, HIV, Coxsackie virus, Syphilis
• II. SLE, Reiter’s syndrome, Spondyloarthropathies (Ankylosing
spondylitis), JRA, Psoriatic arthritis
• III. IBD (UC or CD) or Celiac disease
• IV. Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis
syndrome (PFAPA) or Cyclic Neutropenia
• V. Multiple sclerosis
• VI. Erythema multiforme/Stevens-Johnson syndrome
• VII. Pyoderma gangrenosum
• VIII. Sweet’s syndrome (acute febrile neutrophilic dermatosis)