POLYARTERITIS NODOSA

Behcet syndrome is a multisystem disorder that usually presents with recurrent oral and genital ulcers. Onefourth of patients develop superficial or deep vein thrombophlebitis. Iritis, uveitis, and nondeforming arthritis may also occur. The 50-year-old drug abuser also has a multisystem disease, including systemic complaints, hypertension, skin lesions, neuropathy, and an abnormal urine sediment. This complex suggests a vasculitis, particularly polyarteritis nodosa. The disease is a necrotizing vasculitis of small and medium muscular arteries. The pathology of the kidney includes an arteritis and, in some cases, a glomerulitis. Nodular skin lesions show vasculitis on biopsy. The 19-year-old with low back pain, morning stiffness, and eye pain has complaints that suggest ankylosing spondylitis. This is an inflammatory disorder that affects the axial skeleton. It is an autoimmune disorder that has a close association with HLA-B27 histocompatibility antigen. Anterior uveitis is the most common extraarticular complaint. Aortic regurgitation occurs in a few percent of patients.

The elderly male presents with nonspecific joint complaints typical of polymyalgia rheumatica. The high erythrocyte sedimentation rate is characteristic. The transient loss of vision suggests concomitant temporal arteritis, an important association seen particularly.

The 50-year-old gentleman is a drug abuser and also has a multisystem disease, including systemic complaints, hypertension, skin lesions, neuropathy, and an abnormal urine sediment. This complex suggests a vasculitis, particularly polyarteritis nodosa. 20 to 30% of patients have hepatitis B antigenemia. The disease is  a  necrotizing vasculitis of  small and  medium muscular arteries. The pathology of the kidney includes an arteritis and, in some cases, a glomerulitis. Nodular skin lesions show vasculitis on biopsy.

Giant cell arteritis

REF: Harrison’s 18′ ed chapter 53 table 54-16

“Giant cell arteritis being a large vessel vasculitis does not cause any purpura”

CAUSES OF PURPURA:

Fibrinoid necrosis is a type of connective tissue necrosis seen particularly in autoimmune diseases (eg, rheumatic fever, polyarteritis nodosa, and systemic lupus erythematosus).

Collagen and smooth muscle in the media of blood vessels are especially involved.

Fibrinoid necrosis of arterioles also occurs in accelerated (malignant) hypertension.

Polyarteritis nodosa (PAN)

• It is a multisystem, necrotizing vasculitis of small and medium-sized muscular arteries.
• Involvement of the renal and visceral arteries is characteristic.
• PAN does not involve pulmonary arteries, although bronchial vessels may be involved;
• Granulomas, significant eosinophilia, and an allergic diathesis are not observed.

Ref: Harrisons principles of internal medicine, 18th edition, Page: 2794.

The risk of developing pre–eclampsia is only mild in chronic glomerulo nephritis and polycystic kidney disease.

The risk is mild to moderate in Renal artery stenosis and severe in Polyarteritis nodosa.

Ans.B

The clinical presentation of the patient in question is consistent with a diagnosis of Polyarteritis Nodosa.

The clinical presentation of the patient in question gives us the following ‘leads’ in approaching the diagnosis.

• Digital gangrene in the setting of normal peripheral pulses.
• Presence of hypertension
• Negative antinuclear antibodies
• Negative anti-dsDNA
• Negative ANCA

Polyarteritis Nodosa: PAN

• Classic Polyarteritis nodosa is characterized by necrotizing inflammation of medium-sized muscular arteries.
• In classic Polyarteritis Nodosa, skin findings include livedo reticularis, subcutaneous nodules, and skin ulcers. Digital gangrene is not an unusual occurrence – CMDT
• Involvement of renal arteries leads to renin mediated hypertension
• Patients with classic PAN are ANCA negative – CMDT
• Positive ANCA (pANCA) are found in low percentage (< 20%) of patients with classical PAN- Harrison [ANCAs that produce a p-ANCA pattern on immunofluorescence testing are frequently associated with microscopic polyangiitis and not classical PAN.
• Polyarteritis nodosa is a term given to necrotizing arteritis of medium-sized vessels. – CMDT
• Microscopic polyangiitis may involve medium-sized as well as small blood vessels and its spectrum overlaps that of PAN.
• The clinical presentation of the patient in question is consistent with a diagnosis of PAN.

Takayasu’s disease is also known as ‘pulseless disease’ and absence of peripheral pulses is a clinical hallmark of the disease. The presence of all peripheral pulses makes this diagnosis unlikely.

SLE: Absence of ANA and Anti ds- DNA almost rules out the possibility of SLE as a probable diagnosis.

Wegener’s granulomatosis is a necrotizing granulomatous vasculitis of small arteries and skin manifestations do not include digital gangrene.

Antineutrophil cytoplasmic antibodies (ANCA) occur is about 90% of patients with active Wegner’s granulomatosis.

Absence of ANCA in blood strongly points against a diagnosis of Wegener’s granulomatosis.

Patient in the question is suffering from hypertension, digital infarcts in presence of palpable peripheral pulses and urine examination showing proteinuria and hematuria.

All of these are features of polyarteritis nodosa a necrotizing vasculitis of small and medium-sized muscular arteries with characteristic involvement of the renal and visceral arteries.

It does not involve pulmonary arteries, sometimes bronchial vessels may be involved.

Clinical features: Patients presents with fever, weight loss, and malaise, headache, abdominal pain and myalgias. Renal involvement manifests as hypertension, renal insufficiency, or hemorrhage due to microaneurysms.

Investigations: CBC shows neutrophilic leucocytosis, anemia of chronic disease and an elevated ESR. Antibodies against myeloperoxidase or proteinase-3 (ANCA) is rarely found. Urine shows evidence of proteinuria and hematuria.

Diagnosis is made by the biopsy of the organ involved, which shows evidence of vasculitis.

Ref: Harrison’s Internal Medicine, 18th Edition, Chapter 283; Current Rheumatology Diagnosis and Treatment By John B. Imboden, 2nd Edition, Chapter 33

Differential diagnosis of palpable purpura includes Henoch-Schonlein purpura (HSP), cryoglobulinemia or cryofibrinogenemia, polyarteritis nodosa (PAN), Wegener’s granulomatosis, infections, and collagen vascular disorders.

Giant cell arteritis being a large vessel vasculitis does not cause any purpura.

Answer is B (Lung):

‘PAN (classic PAN) does not involve pulmonary arteries although bronchial vessels may be involved. Aneurysmal dilatation npto 1 cm in size along the involved arteries is characteristic of PAN.^r-Harrison 16th/2007.

Classical PAN: Review

Classical PAN is a multisystem necrotizing vasculitis of small & medium sized muscular arteries in which involvement of renal & visceral arteries is characteristic

Clinical Manifestations Related to Organ System Involvement in Classic Polyarteritis Nodosa

Remember:

• Classic PAN does not involve pulmonary arteries. Bronchial vessels may be involved but their involvement also, is an uncommon Jeature.Q
• Renal involvement is characterized by arteritis without glomerulonephritis. Clinically renal involvement is in the form of renovascular hypertension is frequent. Renal failure may occur but it is uncommon and usually occurs late.Q

Answer is A (Polyarteritis nodosa):

Answer is B (Polyarteritis Nodosa)

The clinical presentation of the patient in question is consistent with a diagnosis of Polyarteritis Nodosa.

The clinical presentation of patient in question gives us the following ‘leads’ in approaching the diagnosis.

• Digital gangrene in the setting of normal peripheral pulses.
• Presence of hypertension
• Negative antinuclear antibodies
• Negative anti dsDNA
• Negative ANCA

Polvarteritis Nodosa: PAN

• Classic Polyarteritis nodosa is characterized by necrotizing inflammation of medium sized muscular arteries.
• In classic Polyarteritis Nodosa, skin findings include livido reticularis, subcutaneous nodules and skin ulcers. Digital gangrene() is not an unusual occurance — CMDT/ 2004/813
• Involvement of renal arteries leads to renin mediated hypertension().
• Patients with classic PAN are ANCA negative — CMDT 2004/814
• Positive ANCA (pANCA) are found in low percentage (< 20%) of patients with classical PAN- Harrison [ANCAs that produce a
  p-ANCA pattern on immunofluorescence testing are frequently associated with microscopic polyangitis and not classical PAN.
• Polyarteritis nodosa is a term given to necrotizing arteritis of medium sized vessels. CMDT 2004
• Microscopic polyangitis may involve medium sized as well as small blood vessels and its spectrum overlaps that of PAN.
• The clinical presentation of patient in question is consistent with a diagnosis of PAN.

Takayasu’s disease is also known as `pulseless disease’ and absence of peripheral pulses is a clinical hallmark of disease. The presence of all peripheral pulses makes this diagnosis unlikely.

SLE: Absence of ANA and Anti ds DNA almost rules out the possibility of SLE as a probable diagnosis.

Wegener’s granulomatosis is a necrotizing granulomatous vasculitis of small arteries and skin manifestations does not include digital gangrene.

Antineutrophil cytoplasmic antibodies (ANCA) occur is about 90% of patients with active Wegner’s granulomatosis. Absence of ANCA in blood strongly points against a diagnosis of Wegener’s granulomatosis

Ans. is B i.e. (Polyarteritis nodosa)

Polyarteritis nodosa is the single best answer amongst the options provided.

• Numbness of multiple limbs indicates peripheral neuropathy / mononeuritis multiplex. `PAN is amongst the forms of vasculitis most commonly associated with vasculitic neuropathy’- CMDT.
• Digital zangrene forms part of the typical skin findings in PAN.

`Typical skin findings in PAN include Livido Reticularis, subcutaneous nodules and skin ulcers. Digital gangrene is not uncommon’ – Harrison

• Hypertension (BP = 160/110mmHg) is a common manifestation of renal involvement in PAN.

`Involvement of renal arteries leads to a renin mediated hypertension (much less characteristic of vasculitides involving smaller vessels).

• Renal function may be normal unless renal failure supervenes which is often late in the course of classic PAN.

Also microscopic haematuria though uncommon with renal involvement in PAN may well be seen from haemorrhage due to microaneurysms. Harrison 16¹¹¹ /2007

(Remember that pathology in the kidney in classic PAN is that of Arteritis without Glomerulonephritis). PAN is the answer of choice as if satisfies most diagnostic hint provided in the question.

Answer is A (Tuberculosis):

Tuberculosis is not mentioned as a cause of peripheral neuropathy

Diabetic Mellitus, SLE, PAN and sarcoidosis may all cause peripheral neuropathies.

SLE can cause a distal symmetric sensory or sensorimotor neuropathy and rarely monouritis multiplex.

— Current Neurology Pt/.318 Sarcoidosis may cause a diffuse sensorimotor neuropathy – Current Neurology 1S`/318

PAN may be associated with mononeuropathy multiplex – Current Neurology 1×1/318

Ans. is ‘c’ i.e., Polyatrteritis nodosa

The hepatitis B surface antigen is present in 25% of patients with Polyarteritis Nodosa.

Hepatitis C antibody is present in patients with essential mixed cryoglobinuria and rarely in patients with poly arteritis nodosa.

Ans. is ‘a’ i.e., PAN

• Among the given options, PAN is predominantly necrotizing vasculitis, characterized by fibrinoid necrosis.
  • During acute phase of PAN, there is transmural inflammation with mixed infiltrate of neutrophils, eosinophils and mononuclear cells with accompanied fibrinoid necrosis.
  • Other three options are predominantly granulomatous vasculitis.