1.

Dasar Imunologi @Annisanurul @ajeng @wahyu

2. Reaksi anafilaksis @Ajeng🌸 @Ratna
3. Reaksi hipersensitivitas @Dinda @Dinul @virginiaviolasp
4. Demam rheuma @Atina @wahyu @rahma
5. LSE @ichlasul @Dika
6. Polimialgia reumatik @Annisanurul @Febri
7. Juvenil kronik arthritis @virginiaviolasp
8. Henoch schoenlein purpura @Ganes @DIka @febri
9. eritema multiformis @Wahyu @Ratna
10. imunodeficiency @Dinul @Dinda
11. Poliarthritis nodusa @Atina @rahma
12. Tindakan Preventif penyakit imunologi @Febri @ichlasul

ACUTE RHEUMATIC FEVER

DEFINITION
Acute rheumatic fever (ARF) is an autoimmune inflammatory process that develops
as a sequela of streptococcal infection. Persons who have experienced an episode of ARF
are predisposed to recurrence following subsequent (rheumatogenic) group A streptococcal
infections.

PATOPHYSIOLOGY
- ARF is characterized by nonsuppurative inflammatory lesions of the joints, heart,
subcutaneous tissue, and central nervous system.
- in developed countries, rheumatic fever follows pharyngeal infection with
rheumatogenic group A streptococci.
- The risk of developing rheumatic fever after an episode of streptococcal pharyngitis
has been estimated at 0.3-3%.
- Two basic theories have been postulated to explain the development of ARF and its
sequelae following group A streptococcal infection:
(1) a toxic effect produced by an extracellular toxin of group A streptococci on
target organs such as the myocardium, valves, synovium, and brain and
(2) an abnormal immune response to streptococcal components. This probably
occurs through molecular mimicry, in which the immune response fails to
differentiate between epitopes of the streptococcal pathogen and certain host
tissues.

EPID
- ARF is predominantly a disease of developing countries and is concentrated in areas
of deprivation and crowding.
- Rheumatic fever does not have a clear-cut sexual predilection, although certain
clinical manifestations, such as mitral stenosis and Sydenham chorea, are more
common in females who have gone through puberty.
 - ARF is most common among children aged 5-15 years. It is relatively rare in infants
and uncommon in preschool-aged children. ARF occurs in young adults, but the
incidence of first episodes of ARF falls steadily after adolescence and is rare after age
35 years.

SYMPTOMS
Rheumatic fever manifests as various signs and symptoms that may occur alone or in
various combinations.
Sore throat
- only 35%-60% of patients with rheumatic fever recall having any upper respiratory
symptoms in the preceding several weeks. Many symptomatic individuals do not
seek medical attention, go undiagnosed, or do not take the prescribed antibiotic for
acute rheumatic fever (ARF) prevention.
- If a course of penicillin or another appropriate antibiotic is taken at this time, the
risk of ARF is reduced by approximately 80%. [17]
Arthritis
- Overall, arthritis occurs in approximately 75% of first attacks of ARF. The likelihood
increases with the age of the patient, and arthritis is a major manifestation of ARF in
92% of adults.
- The arthritis of ARF is usually symmetrical and involves large joints, such as the
knees, ankles, elbows, and wrists
Carditis
- Of first attacks of ARF, carditis occurs in 30%-60% of cases. It is more common in
younger children but does occur in adults.
- Patients with carditis may present with shortness of breath, dyspnea upon exertion,
cough, paroxysmal nocturnal dyspnea, chest pain, and/or orthopnea. Carditis may
also be asymptomatic and may be diagnosed solely via auscultation or
echocardiography.
Sydenham chorea
- This occurs in up to 25% of ARF cases in children but is very rare in adults. It is more
common in girls
- It typically presents 1-6 months after the precipitating streptococcal infection
Erythema marginatum
- In first attacks of ARF in children, erythema marginatum occurs in approximately
10%. Like chorea, it is very rare in adults.
- Patients or parents may report a nonpruritic, painless, serpiginous, erythematous
eruption on the trunk
Subcutaneous nodules
- Subcutaneous nodules are rarely noticed by the patient
Other symptoms
- Other symptoms may include fever, abdominal pain, arthralgia, malaise, and
epistaxis.
CAUSES
- Group A beta-hemolytic streptococcal infection may lead to rheumatic fever BUT
that not all serotypes of group A streptococci cause rheumatic fever.
- some strains (eg, M types 4, 2, 12) in a population susceptible to rheumatic disease
do not result in recurrences of rheumatic fever.
- The classic rheumatogenic serotypes are thought to include 3, 5, 6, 14, 18, 19, and
24.
- More recent data, largely from studies of the indigenous peoples of Australia,
suggest that skin infections (pyoderma) can predispose to ARF and that various other
serotypes may be involved.

LABORATORY
Throat culture
- Throat culture remains the criterion standard for confirmation of group A
streptococcal infection.
- Rapid antigen detection tests are not as sensitive.
- If a rapid antigen detection test result is negative, obtain a throat culture in patients
with suspected rheumatic fever.
- On the other hand, because of the high specificity of these tests, a positive rapid
antigen test confirms a streptococcal infection.
Antibody titer tests
- Antibody titer tests used include ASO test, antistreptococcal DNAse B (ADB) test, and
the antistreptococcal hyaluronidase (AH) test.
- ASO is a test used to detect streptococcal antibodies directed against streptococcal
lysin O.
- An elevated titer is proof of a previous streptococcal infection. It is usually more
elevated after a pharyngeal than skin infection, while the ADB is typically elevated
regardless of the site of the infection
Blood cultures
- Blood cultures are obtained to help rule out infective endocarditis, bacteremia, and
disseminated gonococcal infection.

Imaging Studies
Chest radiography
- Chest radiography can reveal cardiomegaly and CHF in patients with carditis.
Echocardiography
- Echocardiography may demonstrate valvular regurgitant lesions in patients with ARF
who do not have overt clinical manifestations of carditis.
- Patients with echocardiographically diagnosed subclinical carditis cases should
receive the same long-term penicillin prophylaxis as those with the more classic
 clinical carditis,since they are also at risk for poor outcomes due to recurrent
rheumatic heart disease.
- Valvular stenotic lesions, especially of the mitral valve, can be observed in rheumatic
heart disease.

Histologic Findings
Rheumatic fever is characterized pathologically by exudative and proliferative inflammatory
lesions of the connective tissue in the heart, joints, blood vessels, and subcutaneous tissue.
- In the early stage, fragmentation of collagen fibers, cellular infiltration that is
predominantly lymphocytic, and fibrinoid deposition followed by the appearance of
a myocardial Aschoff nodule (a perivascular focus of inflammation that has an area
of central necrosis surrounded by a rosette of large mononuclear and giant
multinuclear cells) occur. The nuclei of these cells resemble owl eyes and are called
Anichkov cells.
- Subcutaneous nodules histologically resemble Aschoff nodules. The brain may show
scattered areas of arteritis and petechial hemorrhages, which have an uncertain
relationship to Sydenham chorea.
Diagnosis
Jones Criteria, 2015 revision, low-risk populations (United States, Europe, other high-income
areas)
Major criteria are as follows:
 Carditis (clinical or echocardiographic diagnosis)
 Polyarthritis (not monoarthritis)
 Chorea (rare in adults)
 Erythema marginatum (uncommon; rare in adults)
 Subcutaneous nodules (uncommon; rare in adults)
Minor criteria are as follows:
 Polyarthralgia (cannot count arthritis as a major criterion and arthralgia as a minor
criterion)
 Fever exceeding 38.5°C
 Elevated ESR (>60 mm/hr) or CRP level (>3 mg/L)
 Prolonged PR interval

Jones criteria, 2015 revision, high-risk populations (Oceania, Africa, South Asia, other lower-
income areas)
Major criteria are as follows:
 Carditis (clinical or echocardiographic diagnosis)
 Polyarthritis or monoarthritis: Polyarthralgias can be considered only after careful
consideration of the differential diagnoses.
 Chorea (rare in adults)
 Erythema marginatum (uncommon; rare in adults)
 Subcutaneous nodules (uncommon; rare in adults)
Minor criteria are as follows:
 Polyarthralgia (cannot count arthritis as a major criterion and arthralgia as a minor
criterion)
 Fever exceeding 38°C (note lower cutoff)
  Elevated ESR (>30 mm/hr; note lower ESR standard) or CRP level (>3 mg/L)
 Prolonged PR interval

Recurrent ARF can be diagnosed based on 2 major, 1 major plus 2 minor, or 3 minor criteria.

MEDICAL CARE
Management and prevention of acute rheumatic fever (ARF) can be divided into the
following 4 approaches.
1. Treatment of the group A streptococcal infection that led to the disease
Although never proven to improve the one-year outcome, this is a standard practice. It may
at least serve to reduce the spread of rheumatogenic strains.
2. General treatment of the acute episode
- Anti-inflammatory agents are used to control the arthritis, fever, and other acute
symptoms.
- Bed rest is a traditional part of ARF therapy and is especially important in those with
carditis. Patients are typically advised to rest through the acute illness and to then
gradually increase activity
- Intravenous immunoglobulin has not been shown to reduce the risk of rheumatic
heart disease or to substantially improve the clinical course.
- IV immunoglobulin, steroids, and plasmapheresis have all been used successfully in
refractory chorea, although conclusive evidence of their efficacy is limited.
- Some early but promising work suggests a possible role for hydroxychloroquine in
the treatment of ARF, although no clinical data are yet available to recommend its
use.
3. Cardiac management
- Bedrest is essential in patients with cardiac involvement.
- Carditis resulting in heart failure is treated with conventional measures; some use
corticosteroids for severe carditis, although data to support this are scant.
- Diuretics and vasodilators are the mainstays of therapy.
- Monitor for development of arrhythmias in patients with active myocarditis.
4. Prophylaxis

SURGICAL CARE
Surgical care is not typically indicated in ARF. Surgical intervention is required only to treat
long-term valvular cardiac sequelae of ARF that cause stenosis.

COMPLICATIONS
A. Immediate complications
- Pancarditis that causes CHF, heart blocks, or pericardial effusion requires emergent
inpatient care and cardiology evaluation.
- Chorea can present months after the inciting infection and can be quite debilitating.
B. Long-term sequelae
 - The only long-term sequela is rheumatic heart disease, which can present years later
as valvular stenosis, most commonly involving the mitral valve.
- These patients are prone to infective endocarditis and stroke.
- Valvular stenosis can lead to heart failure and may require surgery.

Prognosis
- The prognosis of ARF has been improved by preventing recurrent attacks with
secondary antimicrobial prophylaxis.
- the overall prognosis is worse in those with severe carditis at first presentation, and
most develop significant rheumatic heart disease.

POLYARTERITIS NODOSA

Classic polyarteritis nodosa (PAN or c-PAN) is a systemic vasculitis characterized by

necrotizing inflammatory lesions that affect medium-sized and small muscular arteries,
preferentially at vessel bifurcations. These lesions result in microaneurysm formation,
aneurysmal rupture with hemorrhage, thrombosis, and, consequently, organ ischemia or
infarction.

Pathophysiology
Polyarteritis nodosa (PAN) spares large vessels (the aorta and its major branches), the
smallest vessels (capillaries and small arterioles), and the venous system.Vascular lesions
affect medium-sized muscular arteries and occur mainly at bifurcations and branch points.
Inflammation may start in the vessel intima and progress to include the entire arterial wall,
destroying the internal and external elastic lamina, resulting in fibrinoid necrosis. Aneurysms
develop in the weakened vessel, carrying a subsequent risk for a Thrombi may develop at
the site of the lesions. As lesions progress, proliferation of the intima or media may result in
obstruction and subsequent tissue ischemia or infarction.

Etiology
Hepatitis B and PAN
- Hepatitis B virus (HBV) infection is strongly linked with PAN.
- Impaired function of endothelial cells may be part of idiopathic PAN or a
consequence of it; in HBV-PAN, virus replication may directly injure the vessel wall.
Endothelial dysfunction can perpetuate the inflammation through cytokine and
adhesion molecule production.
HBV-associated vasculitis almost always takes the form of PAN. HBV-PAN may occur at any
time during the course of acute or chronic hepatitis B infection, although it typically occurs
within 6 months of infection.
The activity of HBV-PAN does not parallel that of the hepatitis, and symptoms are the same
as those of idiopathic PAN. Small studies have found that gastrointestinal manifestations,
malignant hypertension, renal infarction, and orchiepididymitis were more common in HBV-
PAN.
- HBV was once the cause of up to 30% of PAN cases.Widespread use of the hepatitis
B vaccine has significantly decreased the incidence of HBV-PAN, which is now
estimated to account for less than 8% of all PAN cases.
Genetic associations
- Loss-of-function mutations in CECR1 (alsoknown as ADA2), the gene that encodes
adenosine deaminase 2 (ADA2), have been associated with a spectrum of vascular
and inflammatory phenotypes that includes polyarteritis nodosa.
- Possible roles of ADA2 include regulation of the proliferation of activated T cells and
macrophages and the differentiation of monocytes to macrophages.
- Reduction in ADA2 activity may affect the adenosine inflammatory-response
pathway.
Epidemiology
Occurrence in the United States
Polyarteritis nodosa (PAN) is a rare disease, with an incidence of about 3-4.5 cases per
100,000 population annually. Older estimates placed the prevalence as high as 7.7 cases per
100,000 population, for example, in a population of Alaskan Eskimos hyperendemic for HBV
infection.
Sex- and age-related demographics
- PAN affects men more frequently than women (male-to-female ratio 1.6-2:1).
- PAN has been diagnosed in persons of every age; however, it is predominantly
observed in individuals aged approximately 45-65 years.

History
Polyarteritis nodosa (PAN) is an acute multisystem disease with a relatively short prodrome
(ie, weeks to months). The spectrum of disease ranges from single-organ involvement to
fulminant polyvisceral failure. Common historical features of PAN include the following:
1. Constitutional and musculoskeletal symptoms
 Fever
 Malaise
 Fatigue
 Anorexia and weight loss
 Myalgia
 Arthralgia in large joints or, less commonly, arthritis
2. Central nervous system symptoms
- Transient symptoms of cerebral ischemia, including typical spells of transient
monocular blindness, are the most common presenting CNS deficits of PAN.
- Cerebral arteritis usually presents late in the course of the disease, usually in the
second to third year of the vasculitis.
 - Cerebral arteritis may cause arterial thrombosis with cerebral ischemia or
intraparenchymal or subarachnoid hemorrhage.
- Although CNS lesions usually occur 2-3 years after the onset of PAN, earlier CNS
involvement has been reported.
3. Peripheral nervous system symptoms
- Peripheral neuropathy develops in as many as 60% of patients.
- Vasculitic neuropathy is often asymmetrical and presents as (1) mononeuritis
multiplex, (2) distal polyneuropathy, or (3) cutaneous neuropathy. It can take the
form of a pure motor, pure sensory, or mixed sensorimotor polyneuropathy.
4. Cutaneous symptoms
Dermatologic symptoms are very common in PAN, and about 40% of patients manifest with
skin lesions including rash, purpura, gangrene, nodules, cutaneous infarcts, livido reticularis,
and Raynaud phenomenon. Skin involvement, which can be painful, occurs most frequently
on the legs.
5. Gastrointestinal symptoms
- GI involvement usually presents as nonspecific symptoms and signs such as
abdominal pain (which may be postprandial) and nausea and vomiting, with or
without obvious GI bleeding.
- Rare and more serious complications of PAN include bowel infarction and
perforation, cholecystitis, hepatic infarction, or pancreatic infarction.
6. Renal symptoms
- About 60% of patients with PAN have renal involvement.
- Flank pain may be present.
- Ischemic changes in the glomeruli and renal artery vasculitis can cause renal failure,
hypertension, or both.
- A small percentage of patients may require dialysis.
Additional symptoms
Less common symptoms reported in PAN include the following:
 Genitourinary - Patients may develop pain over the testicular or ovarian area. In rare
cases, testicular infarction may occur; testicular pain is usually unilateral
 Cardiac - Chest pain, dyspnea, palpitations, pericarditis, myocardial infarction, and
congestive heart failure; cardiac disease affects 35% of patients with PAN, but most
affected patients are asymptomatic
 Ophthalmologic - Blurred vision
 Neuropsychiatric - Headache, psychosis and depression

LABORATORY STUDIES
Laboratory findings in PAN are nonspecific but can help to establish the systemic nature of
the disease. Findings include the following:
  Elevated erythrocyte sedimentation rate (ESR) and/or C-reactive protein - These
markers may be useful in evaluating some patients for active disease but do not
correlate with activity in all patients
 Leukocytosis, normochromic anemia, or thrombocytosis
 Hepatitis B surface antigen and hepatitic C serologies
 Elevated creatinine level
 Mild proteinuria
 Elevated levels of liver enzymes
 Hypergammaglobulinemia - Found in 30% of patients with PAN

Imaging Studies
Angiography
Positive findings include aneurysms and stenoses of medium-sized vessels. (Note that these
findings are not pathognomonic for PAN but rarely occur in MPA).
Aneurysms are most commonly found in the kidney, liver, and mesenteric arteries, and their
presence is associated with more severe and extensive disease.

Biopsy
- The most accessible tissue sites for biopsy include the skin, sural nerve, testes, and
skeletal muscle.
- The results of a retrospective study suggest muscle biopsy may be helpful for the
diagnosis of systemic vasculitides, even in the absence of myalgias or creatine kinase
level elevation.

Histologic Findings
When an inflammatory infiltrate is present around a vessel wall without necrotizing
changes, features on nerve biopsy that strongly suggest angiopathic nerve injury include
Wallerian degeneration and fiber loss in part of a fascicle, perineural necrosis, and
neoangiogenesis around the epineurium or perineurium. An occlusion of a muscular artery
and leukocytic infiltrate is seen in the slide below.
Approach Considerations
The treatment of polyarteritis nodosa (PAN) has improved dramatically. Previously,
untreated PAN was usually fatal within weeks to months, with mortality often associated
with kidney failure, cardiac complications, or gastrointestinal (GI) complications. Therefore,
early diagnosis and treatment are critical in PAN.
- Currently, corticosteroids are the cornerstone of treatment. The addition of
cyclophosphamide is the standard of care for patients with idiopathic PAN whose
disease is steroid refractory or includes major organ involvement. This combination
can provide prolonged survival for these patients.
- Cyclophosphamide is not routinely recommended in hepatitis B–related PAN, as the
use of steroids with cyclophosphamide in these patients has been demonstrated to
enhance viral replication. Instead, treatment for hepatitis B–related PAN consists of
schemes that include corticosteroids with antiviral agents and plasmapheresis.
Antiviral drugs used include vidarabine or interferon alpha-2b.
- Biologic agents have been investigated in patients with steroid-refractory and
recurrent PAN. Case reports have described response to treatment with tumor
necrosis factor inhibitors,including infliximab and etanercept.
- The interleukin-6 antagonist tocilizumab has been used successfully in refractory
cases.
- Successful use of the anti-CD20 agent rituximab in an adult with refractory PAN has
also been reported.
- Plasma exchange has been used in a few patients with severe PAN.
Surgical care
Surgery may be necessary for GI manifestations of PAN, including bowel ischemia,
cholecystitis, and appendicitis. Microcoil embolization of cerebral aneurysm may be
indicated. Postsurgical care may be needed for patients with PAN who develop bowel
infarction.