​Kembara Xtra - Medicine - Polyarteritis Nodosa

​Kembara Xtra - Medicine - Polyarteritis Nodosa 
Antineutrophil cytoplasmic antibody (ANCA)-negative necrotizing arteritis of medium-sized muscle arteries and (rarely) tiny arteries is known as polyarteritis nodosa (PAN).
Capillaries, venules, and arterioles remain unaffected.
GI tract, peripheral nervous system (sensory and motor), CNS, genitourinary, skin, and cardiovascular systems are among the affected ones.
Both pulmonary capillaritis and glomerulonephritis are uncommon.
Features vary according to the location of the vasculitis and may include purpuric or nodular skin lesions, livedo reticularis, new-onset or worsening hypertension (HTN), and mononeuritis multiplex.
● HTN and a mild case of proteinuria, with or without azotemia, are the typical signs of renal illness in PAN. There could potentially be renal infarction.
PAN used to refer to a number of distinct conditions, including classic PAN, microscopic PAN, and cutaneous PAN. Microscopic PAN appears to be pathophysiologically independent to the other two based on ANCA tests.
- Clinical manifestations of idiopathic generalized PAN (classic PAN) might range from single organ involvement to polyvisceral failure.
- Patients with HBV-associated PAN have active hepatitis B infection and can present with symptoms comparable to those of idiopathic generalized PAN.
- Microscopic polyangiitis (MPA) (small arteriole involvement) and ANCAs directed against myeloperoxidase (MPO) characterize microscopic PAN. This is now categorized as vasculitis linked with ANCA.
- Limited or cutaneous PAN often only affects the deep dermal and subcutaneous (SC) regions of the skin and has distinctive histopathologic characteristics.
Although myalgias, peripheral motor neuropathy (mononeuritis multiplex), or sensory neuropathy may be present, there aren't many systemic symptoms.
Synonyms include necrotizing arteritis, periarteritis, and panarteritis.


Predominant age: peaks in the fifth to sixth decade; incidence increases with age. Epidemiology Incidence: Incidence of 0 to 1.6 cases per million.
50 is the average age at diagnosis.
 Predominance of men

Rare: up to 31 occurrences per 1 million adult population


Pathophysiology and Etiology 
Aneurysm formation at vessel bifurcations; segmental, transmural, necrotizing inflammation of the medium and small muscle arteries; intimal proliferation; thrombosis; and ischemia of the endorgan/tissue supplied by the afflicted vessels.
The majority of hepatitis B-related PAN cases are idiopathic; 20% are linked to hepatitis B or C infection. Hepatitis B-related PAN causes direct vascular injury as a result of viral replication or immune complex deposition, with complement activation and a subsequent inflammatory response. The implicated vessel walls of patients with PAN and hepatitis B have yielded HBsAg.
Adenosine deaminase 2 (ADA 2) genetic mutations have been discovered in families with PAN.


Hepatitis B infection is more dangerous than hepatitis C infection (cutaneous PAN)

Accompanying Conditions 

Hairy cell leukemia, Hepatitis B (high relationship with classic PAN), Hepatitis C (less significantly associated with cutaneous PAN),
Following hepatitis B vaccination, there were 27 occurrences of systemic PAN treated with minocycline (symptoms disappear when drug is stopped; recur if drug is taken again).
 Case-based correlations with amphetamines, interferon, and CMV infection

No formal diagnostic criteria exist for PAN, therefore suspect PAN if you have: - Acute, occasionally fulminant multisystem disease with a brief prodrome (i.e., weeks to months)
- Sensorimotor symptoms/findings associated with a vascular skin rash
- HTN with systemic symptoms that just started.
- Systemic symptoms associated with sensory and/or motor neuropathy that is unknown.
- Multisystem illness brought on by hepatitis B infection

History 

The symptoms are a direct result of organ involvement.
 Constitutional signs (fever, loss of appetite, and malaise)
 Symptoms specific to an organ
- Myalgia and arthralgia - Focal muscular weakness/extremity numbness
- Nodules, purpura, and rash
- Constant postprandial discomfort, intestinal angina, dizziness, nausea, and bleeding
- Headaches, migraines, and multiple mononeuritis
- Neurogenic bladder, testicular/epididymal discomfort (rare)

clinical assessment 

Results and curriculum show precise organ involvement.
Peripheral nerve system: mononeuritis multiplex, peripheral neuropathy
RENERAL: HTN
Skin conditions include livedo reticularis, purpura, urticaria, polymorphic rashes, SC nodules (rare but distinctive), deep skin ulcers, particularly in the lower extremities, Raynaud's phenomenon, and single-digit gangrene.
GI: discomfort, rebound, and acute abdomen
convulsions, altered mental status, and papillitis in the CNS. Pleural effusion symptoms in the lungs, including reduced breath sounds and dullness to percussion.
Cardiac: S3 gallop; pericarditis; indications of congestive heart failure and/or myocardial infarction (friction rub is uncommon).
Testicular and epididymal tenderness (which can mimic testicular torsion)
arthritis, which typically affects big joints in the lower extremities.


Differential Diagnosis Other types of vasculitis (ANCA-associated, including Henoch-Schönlein purpura, drug-induced vasculitis, cryoglobulinemia, and Goodpasture syndrome; granulomatosis with polyangiitis [GPA] (formerly known as Wegener granulomatosis), Churg-Strauss syndrome, and MPA)
Buerger disease, Systemic lupus erythematosus (SLE), thrombotic disease (antiphospholipid antibody syndrome), embolic disease (atrial myxoma, cholesterol emboli), multiple sclerosis, systemic amyloidosis, infection (subacute endocarditis, HIV infection, trichinosis, rickettsial diseases), calciphylaxis lesions, fibromuscular dysplasia, er


Laboratory Results 

There were no significant abnormalities in the lab. If feasible, use a biopsy to confirm the diagnosis.
Angiography, whether conventional, CT, or MR, can detect microaneurysms as well as the beading of bifurcating blood vessels.
In cases of renal illness, avoid contrast. Nonspecific laboratory abnormalities:
- Increased CRP and ESR
- Moderate proteinuria and increased creatinine
- 10–50% of people have hepatitis B surface antigen positivity.
Hepatitis C virus RNA and antibodies against proteinase 3 (PR3) and MPO are negative. Positive ANCA challenges PAN.
Rheumatoid factor could be favorable.
- A chronic disease's anemia
Initial examinations (lab, imaging)
Check for signs of a systemic illness and rule out any potential causes:
Thrombocytosis on the CBC, high CRP and ESR
Hepatitis B serology is frequently positive; hepatitis C serology is less frequently positive.
LFTs are abnormal if hepatitis B or C is present or if the hepatobiliary tract is involved. Urinalysis reveals proteinuria/hematuria but typically no cellular casts or active urine sediment. 
Cryoglobulins, anti-MPO, anti-PR3, ANA, and ANCA
Complement levels (C3, C4) and angiographic evidence of small- and medium-sized artery aneurysmal alterations and beading


Other/Diagnostic Procedures

 Nerve conduction tests and electromyography in patients with suspected mononeuritis multiplex. Consider a sural nerve biopsy if something is off.
 An arterial or tissue biopsy, which is the least intrusive method.
 Skin biopsy from the borders of ulcers; deep dermis and SC fat to evaluate the involvement of the small muscle artery (excisional not punch biopsy).
Interpretation of Tests
 Segmental, frequently at bifurcations and branchings, necrotizing inflammation with fibrinoid necrosis of small and medium-sized muscle arteries. Capillaritis and other lung parenchymal involvement by vasculitis clearly suggest another process (microscopic PAN, GPA, Churg-Strauss syndrome, or antiglomerular basement membrane disease), as venules are not implicated in classic PAN.
 Acute lesions involving necrosis, thrombosis, and infarction of the affected tissue; infiltration of polymorphonuclear cells through vessel walls into the perivascular area.
 Aortic dissection and other aneurysmal dilatations
Vasa nervorum with necrotizing vasculitis: 50–70% peripheral nerves
Muscle vessels: 50%; testicular vessels involved in symptomatic males; GI vessels: 50% (at autopsy) with intestinal necrosis; gallbladder and appendix vasculature: 10%
The primary distinctions between this necrotizing vasculitide and others are the sparing of veins and pulmonary arteries and the absence of granuloma development.


 Management 
Stroke, myocardial infarction, and heart failure are problems that should be aggressively treated to avoid.

First Line of Medicine

Corticosteroids (CS) (high-dose oral prednisone [1 mg/kg/day] or intravenous [IV] methylprednisolone [0.5 to 1.0 g/day] for 3 days, then switch to prednisone 1 mg/kg/day, and taper according to response) are used to treat severe (life-threatening) diseases.
- With CS, only 50% of patients achieve and keep remission. Additional immunosuppressive treatment is necessary for other patients.
- In moderate to severe PAN, IV cyclophosphamide (0.6 g/m2 every two weeks for three doses, then monthly for 4 to 12 months) combined with CS increases survival and prevents the need for chronic steroids.Cyclophosphamide carries a risk of cancer and infertility.
- Plasma exchange for serious illnesses that are resistant to treatment, like chronic kidney diseaseLess severe disease: CS alone vs. additional immunosuppressive drugs (azathioprine 2 mg/kg/day, methotrexate 20–25 mg/week, mycophenolate mofetil 2,000–3,000 mg daily). The usage of hydroxychloroquine (5 mg/kg/day) has been documented.
Dapsone, colchicine, and nonsteroidal anti-inflammatory medications are used to treat cutaneous PAN.
Antiviral medications, short-term CS, and plasma exchange for HBV-associated PAN
Tocilizumab has been noted in PAN that is treatment-resistant and hepatitis B-negative.

Next Line
Infliximab (3 to 5 mg/kg IV at 0, 2, and 6 weeks, and every 4 to 8 weeks thereafter) and rituximab (1,000 mg IV on days 0 and 14 and then every 6 months OR 375 mg/m2 IV weekly for 4 weeks) have both been anecdotally reported to be helpful in refractory PAN. However, there is no clearly defined second-line therapy for PAN.


Further Therapies 

Mercaptoethanesulfonate lowers bladder exposure to carcinogenic metabolites in patients receiving IV cyclophosphamide.
Trimethoprim-sulfamethoxazole should be administered as a preventative measure to patients taking cyclophosphamide for Pneumocystis jiroveci (carinii) pneumonia (use dapsone 100 mg/day or atovaquone 1,500 mg/day in patients who are intolerant or allergic).


Admission is based on the participation of certain organs and their extent.


Patient Follow-Up Monitoring

 tests for the liver, kidney, and CBC as well as urinalysis.
Acute-phase reactants, like ESR and CRP, may be used to track the progression of the illness.
● The 2009 Five Factor Score (FFS) revision can forecast mortality and provide therapeutic approaches. Age, renal failure, cardiac involvement, and GI signs are all taken into account while evaluating PAN patients. Patients with ANCA-associated vasculitis are the only ones who are affected by the fifth component, ENT symptoms.
● Watch out for: - Immunosuppressant drug side effects
- Delayed emergence of tumors, particularly bladder cancer, in cyclophosphamide-treated patients (check annual urinalysis, urine cytology, and urologic assessment if microscopic hematuria).- Osteoporosis brought on by steroids

Dietary recommendations for patients receiving CS therapy include calcium- and vitamin D-rich meals, a low-salt diet (HTN), and the Mediterranean diet.


Poor prognosis is anticipated for PAN that is left untreated.
Treatment with steroids and cytotoxic drugs raises the 5-year survival rate to 75-80% (2).
Since the development of antiviral medications, survival rates for PAN associated with hepatitis B have increased.
The prognosis is poorer for patients who present with proteinuria, renal insufficiency, GI tract involvement, cardiomyopathy, CNS involvement, or who are older than 65.

End-organ damage from ischemia and complications from immunosuppressive medications are complications.

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