Ankylosing spondyloarthritis and IBD
Association between HLA-B27 genotype and Ankylosing Spondylarthritis.
Surely the test for histocompatibility antigen helps to diagnose A.S. (ankylosing
spondyloarthritis), a disease associated with inflammatory bowel disease. 50% of
the subjects that have this marker in combination with Crohn's disease can
develop A.S.
Peripheral enteropathic arthritis is divided into two types:
Type 1 (pauciarticular <5 affected joints.
4.4% of patients, is associated with HLA-B27 in 26% of patients; shows episodes
of oligoarthritis (knees) with a self-limiting character; is associated with
recurrences of IBD (inflammatory bowel disease); it can be associated with other
extraintestinal manifestations; it can precede (like spondylitis) the diagnosis
of IBD.
Type 2 (polyarticular:> or equal to 5 joints: affects 2.9% of patients,
is symmetrical arthritis, affects MCF, has a chronic trend, is independent of
the activity of IBD, is not associated with HLA -B27; it is associated only with
uveitis and rarely precedes the diagnosis of IBD.
Differential diagnosis is imperative with inflammatory low back pain. This has a
sneaky onset, dull pain, difficult to locate, often intermittent and unilateral
in the beginning, pain p more intense at rest, is associated with stiffness of
movement and is lessened with movement, accentuated by coughing and sneezing,
cause asthenia.
The thoracic pain of the inflammatory form is due to enthesitis ie to
inflammation of the cost-vertebral joints, costosternal and dumbbell-sternal.
It is accentuated by coughing and deep breaths; these are episodes of varying
duration, associated with limiting thoracic expansion. You can have "sausage"
fingers and edema of the foot with a sign of typing.
The Achilles tendon may be affected. Extraarticular manifestations are
represented by anterior uveitis in 25%, aortic insufficiency in 4% of cases in a
duration of less than 15 years and aortic insufficiency in 10% of cases in
subjects affected by> 30 years; cardiac conduction may be affected in 3% of
subjects within 15 years and in 9% in subjects after 30 years of duration.
Sacroileite: degrees
0 = normal
I doubt =
II = sclerosis, small erosions
III = sclerosis, gross erosions
IV = ankylosis
IBDs have a genetic predisposition; the genetic background can explain the
dysregulation of the mucosal immune system and the interaction with hostile
bacteria. Some genotype / phenotype correlations, for example, in arthropathies
have been replicated, but there are clinical difficulties and therefore require
prospective studies.
An important role is played by cytokines in mucosal inflammation. They have
interleukins and chemokines, small soluble proteins of just over one hundred
amino acids; they are produced by cells of the immune system and not; induce
proliferation in cells with specific receptors; they are the target of new
biological therapies.
It is admitted that an antigen (bacterial, other?) Can activate the macrophage
cell that processes the antigen and presents it to the native T cell; this, in
turn, under stimulation, produces gamma interferon and stimulates the Th1 which
produces gamma IFN and stimulates the macrophage that produces metalloproteases
and in turn stimulates the fibroblasts.
In addition to this classic route, the one mediated by the Th 17 (see diagram)
has recently been accepted.
However it may be, in the end it results in a mucosal inflammatory damage. A
similar etiopathogenetic mechanism occurs in rheumatoid arthritis, where there
is always the activation of the macrophage by an antigen with stimulation on a T
Naive lymphocyte which in turn stimulates the Th1 and therefore this the
macrophage that through the TNF alpha determines a synovial hyperplasia and bone
tissue destruction by osteoclasts. In IBD the TNF alpha released with a similar
process causes the mucosal damage, through the metalloproteins.
There are new therapeutic targets that are represented by interleukins:
IL-12 plays a role in the activation of Naive T cell, IL23 in the activation
of Th17 and in the maintenance of inflammation.
IL 6 plays a role in the activation of Th17. This is demonstrated because in the
blockade of IL-6 with anti-IL6Ralfa antibodies, it suppresses T-cell resistance
to apoptosis. Finally it must be said that mice with congenital deficiency of
Il-21 are protected towards the development of colitis.
In essence, the subject with inflammatory bowel disease is as if he has a
pattern of intestinal immunological responses to food and bacterial flora
antigens, with loss of tolerance and uncontrolled inflammation.
At this point the intestinal inflammation therapy is based on multiple points of
action. One of these is the role that TNF alfa (tumor necrosis Factor alfa)
plays in the damage, which is blocked by infliximab, adalimumab, CDP 571 ,.
CDP870, etanercept and so on.
The types of biological therapies are: monoclonal antibodies, recombinant
cytokines, growth factors, antisense oligonucleotides, small molecules. Between
etnercept and infliximab, the difference lies in the fact that infliximab causes
apoptosis of inflammatory cells (activated T cells).
Ultimately it is said that the inflammatory response depends on a kind of
balance where inflammatory factors are set: TNFalpha, IL1 beta., IL-17, IL-12,
IFN gamma and IL-4/13 anti-inflammatory factors. IL 1ra, TGF beta, IL-10.
The role of a NOD2 gene in Crohn's disease is also discussed, based on the
transcription of pro-inflammatory mediators. ASCA markers of ankylosing
spondylarthritis and uSpA rather than rheumatoid arthritis. In conclusion, the
articular symptoms in IBD are frequent, often persistent and may even precede
the diagnosis of IBD.
The clinical phenotype differs for RCU and for M. of Crohn. Immunogenticity
predisposes to the type of arthropathy (eg HLA-B27, B35, B44, A1, CARDS15). ASCA
antibodies are associated with IBD and arthropathy. Faecal markers are helpful
in the study and follow-up of IBDs.
Flow chart of the study of heteropathic arthritis.
gangrenous pyoderma
nodular erythema
vasculitis
papulo-pustolosi neutrophils
s. of sweet.
Still psoriasis
Epidermolysis bullosa acquired disease to linear IgATherapy of Crohn's disease
Mild and moderate disease.
Oral steroids (prednisone and m-predisolone
Parenteral steroids
ACTH
Hydrocortisone
m-prednisolone
Topical steroids
Hydrocortisone
Tixocortol P
Budesonide (entocir 3 g, 3 cpr for 8 weeks, then 2 cpr)
beclomethasone
if no answer:
Infliximab e.v.
Adalimumab SC
Cartolizumab SC
to be taken into account:
Antibiotics (metroinidazole-ciprofloxacin)
Immunomodulators (AZA, 6MP)
MTX
Predinisone 0.8 mg / kg for 2 weeks then reduce by 5 mg / week
At the same time AZT up to 2 mg / kg reduced to 1 mg / kg due to increased
cholestasis indices.
The treatment is always under the prescription and control of the
gastroenterologist. Never suspend it or start a treatment without criteria.
indexi gastroenterology