Diagnostic investigations and differential diagnoses

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When cutaneous signs are associated with general symptoms and/or other organ or system involvement of vasculitis, differential diagnoses are primarily other systemic diseases, like systemic lupus erythematosus, and secondary vasculitides, attributed to infections, neoplasia, hematologic malignancies or drugs. Indeed, many drugs have been reported to be potential causative agents of vasculitis (Table 5). Differential diagnoses of isolated purpuric lesions are numerous and relatively easy to make (thrombotic and/or thrombocytope-nic purpuras: idiopathic thrombocytopenic purpura, disseminated intravascular coagulopathy, thrombopathies; vascular purpuras, with exclusion of vasculitides: Ehlers-Danlos disease, scorbut, amyloidosis, Bateman's purpura, etc.). Embolic or atheromatous thromboses should also be ruled out when confronted with isolated distal necrosis or necrotic purpura. McDuffie's hypo-complementemic urticarial vasculitis is a rare systemic disease, characterized by the presence of circulating anti-C1q autoantibodies, mainly IgG, and hypocomplementemia. It preferentially affects women, in their 30 s, and is a vasculitis that involves postcapillary venules. Subacute and recurrent urticarial eruptions, each lasting about 12 h, with usually little pruritus, combined with systemic symptoms and, most characteristically, subacute obstructive pulmonary disease, in 25-65% of the patients, is suggestive of the affection. Histologi-cally, lung manifestations are a consequence of emphysema that is far from usual in other primary vasculitides and in non-smokers. Quincke's edema, arthralgias, pericarditis and proliferative kidney disease that may require immunosuppressive therapy have been reported on several occasions (Schwartz et al., 1982). Schnitzler's syndrome is another chronic urticarial vasculitis, without pruritus and with no complement abnormalities. It is usually associated with bone osteocondensation, IgM paraproteinemia, leukocytoclastic vasculitis and vascular Ig deposits, detected during histolog-ic examination of skin biopsies. Most of the reported cases followed benign courses, but some progressed to Waldenstrom's macroglobulinemia

Table 5

Drugs that have been reported to induce vasculitis

Antibiotics

Chloramphenicol

Clindamycin

Gentamicin

Isoniazid

Macrolides

Penicillin

ß lactams

Fluoroquinolonesa

Rifampicin

Sulfamides

Cyclines

Minocyclinea

Vancomycin

Antiviral agents

Acyclovir

Efavirenz

Indinavir

Zidovudine

Antifungal Griseofulvin

Vaccines

Influenzae

Hepatitis A, B

Pneumococcus

Measles

Rubeola

Diuretics

Chlorthalidone

Furosemide

Hydrochlorothiazide

Spironolactone

Antithyroid drugs Carbimazolea Methimazole Propylthiouracila

Antiepileptic drugs Valproic acid Carbamazepine Phenytoina Trimethadione

Cardiovascular drugs

Acebutolol

Amiodarone

Atenolol

Captopril

Diltiazem

Guanethidine Hydralazinea

Methyl-dopa

Nifedipine

Losartan

Procainamide

Ramipril

Quinidine

Psychotropic medications

Amitriptyline

Clozapinea

Cocaine

Diazepam

Ectasia

Fluoxetine

Heroine

Maprotiline

Paroxetine

Trazodone

Anticoagulants Heparin Streptokinase Warfarin

Growth factors

G-CSF

GM-CSF

Sympathomimetics Ephedrine Methamphetamine Phenylpropanolamine

Leukotriene antagonistsa

Montelukasta

Pranlukasta

Zafirlukasta

Anti-cancer agents and immunosuppressants

Azathioprine

Busulphan

Chlorambucil

Cyclophosphamide

Non-steroidal anti-inflammatory drugs

Aspirin Celecoxib Mefenamate Diclofenac

Table 5 (continued)

Cytosine arabinoside

Flurbiprofen

Melphalan

Ibuprofen

Methotrexate

Indomethacin

Retinoids

Phenylbutazone

Tamoxifen

Piroxicam

Aromatase inhibitors (anastrozole)

Miscellanous

Allopurinola

Cyclosporin A

Potassium iodine

Additives

Dextran

Metformin

Bosentan

Diphenhydramine

Mefloquine

Bromide

D-Penicillaminea

Omeprazole

Cimetidine

Etanercept

Phenacetine

Chlorpropamide

Rituximab

Iodinated contrast agents

Colchicine

Infliximab

Gold therapy for rheumatoid arthritis

Cromolyn

Levamisole

Sirolimus

Sulfasalazinea

Quinine

Tacrolimus

a Drugs that may be associated with the presence of ANCA, predominantly anti-MPO P-ANCA.

a Drugs that may be associated with the presence of ANCA, predominantly anti-MPO P-ANCA.

or non-Hodgkin's lymphoma (Lipsker et al., 2001).

Investigational procedures must therefore be undertaken to confirm or refute the diagnosis of vasculitis, then rule out infections (or identify HBV- or HIV-related PAN, or HCV-mixed cry-oglobulinemic vasculitides, which require specific therapeutic approaches), cancers, hemopathies or drug-induced vasculitis. Medical history and physical examination are essential to making the diagnosis of systemic vasculitis. Assessment of renal, heart and lung functions, and searching for any neurologic manifestation are mandatory. Some laboratory tests and examinations should be performed systematically: differential blood cell counts; coagulation tests; measurement of C-reactive protein, liver enzymes; serum protein electrophoresis; HBV, HCV and HIV serologies; testing for ANCA, cryoglobulinemia, antinuclear antibodies, rheumatoid factor; determinations of complement fractions (C3, C4, HC50); urinary sediment analysis and 24 h-proteinuria evaluation; ECG; and chest X-ray. Other investigations depend on the initial clinical conclusions and the first biological results, like blood hemocultures, other serologic tests (syphilis, streptococcus, cytomegalovirus, parvovirus B19, etc.), echocar-diography, thoracoabdominal or sinus computed tomography scan, brain imaging, lumbar puncture, renal and celiomesenteric angiography, etc. Ideally, histologic confirmation of vasculitis should be obtained in a biopsy of the affected organ or tissue, with indirect immunofluores-cence assay. As mentioned above, skin biopsies often show some abnormalities, especially le-ukocytoclastic vasculitis, which is unfortunately not specific to any of the primary systemic ne-crotizing vasculitides. However, skin biopsies are important to exclude some other diagnoses. Cutaneous lesions with histologically proven granu-lomatous inflammation may also be seen in inflammatory bowel diseases, sarcoidosis, systemic lupus erythematosus or lymphoma. Pertinently, old, scarred and healing skin lesions, especially when they are superinfected, should never be biopsied.

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