Lupus-like syndrome

Hydralazine 4-8 hour Up to 30 minute 5-40 mg prn dosing Headache, tachycardia, lupus like syndrome, potential nephrotoxicity Often given with beta-blocker to counter reflex sympathetic drive, may increase ICP... 

Direct Vasodilators Isosorbide dinitrate 20 mg and hydralazine 37.5 (BiDil) 1-2 tablets three times a day Minoxidil (Loniten) Hydralazine Heart failure (isosorbide dinitrate + hydralazine in African-Americans) A-HeFT66 Edema (minoxidil) Tachycardia Lupus-like syndrome (hydralazine) ... 

Isoniazid Adults S mg/kg (300 mg) Children 1 0-1 S mg/kg (300 mg) Asymptomatic elevation of aminotransferases, clinical hepatitis, fatal hepatitis, peripheral neurotoxicity, CNS system effects, lupus-like syndrome, hypersensitivity, monoamine poisoning, diarrhea LFT monthly in patients who have preexisting liver disease or who develop abnormal liver function that does not require discontinuation of drug Dosage adjustments may be necessary in patients receiving anticonvulsants or warfarin... 

Hydralazine may cause a dose-related, reversible lupus-like syndrome, which is more common in slow acetylators. Lupus-like reactions can usually be avoided by using total daily doses of less than 200 mg. Other hydralazine side effects include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it may be useful in patients with severe chronic kidney disease and in kidney failure. 

Major adverse effects include agranulocytosis (with fever, malaise, gingivitis, oropharyngeal infection, and a granulocyte count less than 250/mm3), aplastic anemia, a lupus-like syndrome, polymyositis, GI intolerance, hepatotoxicity, and hypoprothrombinemia. If it occurs, agranulocytosis almost always develops in the first 3 months of therapy routine monitor-... 

Thiono and sulfhydryl drugs are also associated with a significant incidence of a lupus-like syndrome. Propylthiouracil is associated with a significant incidence of lupus [18] as well as liver toxicity [19, 20] and agranulocytosis [21], Penicillamine is associated with lupus, agranulocytosis [22] and a variety of autoimmune syndromes as discussed later. 

A more recent addition to the list of drugs that have been associated with a lupus-like syndrome is terbinafine [23,24], This drug is also metabolized to a reactive metabolite [25], and it has a very long half-life in the skin, which likely explains why the dominant manifestations of lupus associated with this drug are in the skin. 

Minocycline is associated with a relatively high incidence of hepatotoxicity. In many cases it is quite distinct from minocycline-induced lupus, occurs earlier in the course of treatment (about 1 month), and the mechanism is unknown [62], However, in some cases the liver toxicity merges with the lupus-like syndrome, occurring after about a year of therapy, and is associated with ANA. This form is indistinguishable from idiopathic autoimmune hepatitis [63], and antibodies against Cyp 3A6 and Cyp 2C4 have been reported [64], Diclofenac has also been reported to cause hepatitis with autoimmune features such as ANA [65],... 

The anticonvulsant phenytoin, and to a lesser degree carbamazepine, can inhibit the synthesis of antibodies, and in some cases these drugs can result in lymphoproliferation [77-79]. These effects on the immune system could be viewed as a type of autoimmunity. The relationship between such effects and autoimmunity are still not clear, although the more recent observations that cytokines and anti-cytokines can cause autoimmunity support the existence of such a relationship. The previous edition of this book contained an extensive discussion of the possible relationship between immunosuppression and autoimmunity [80], Phenytoin and carbamazepine can also cause a lupus-like syndrome although the incidence is lower than with many other drugs. 

Possible adverse reactions include fever lupus-like syndrome rise in BUN myalgia septic shock-like syndrome headache asthenia weakness dizziness symptoms of... 

Misceiianeous Brown-black microscopic discoloration of thyroid glands (prolonged therapy), decreased hearing, fever, lupus-like syndrome, secretion discoloration, serum sickness-like syndrome, tinnitus, tooth discoloration, vulvovaginitis. 

Hypersensitivity Anaphylaxis angioedema arthralgia chills drug fever eczematous, erythematous, or maculopapular eruptions lupus-like syndrome associated with pulmonary reactions myalgia pruritus urticaria. 

Autoimmunity Treatment with infliximab therapy may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if a patient develops symptoms suggestive of a lupus-like syndrome following treatment with infliximab. 

Adalimumab is a recombinant, fully human antitumor necrosis factor monoclonal antibody approved in the US and Europe for the treatment of adult patients with moderate to severe, active rheumatoid arthritis. It has to be injected subcutaneously. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. Rare side effects include worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis like neurological disease. 

Lupus-like syndrome more common in "slow acetylators" and following higher doses for prolonged periods... 

Hypersensitivity reaction, lupus-like syndrome, and severe hepatic reactions may... 

Of particular importance in the geriatric patient Weakness, lethargy, dysphoria, inability to concentrate, irritability, dysarthria, dizziness, peripheral neuropathy (dose-related), asymptomatic increase of LFTs, decreased appetite, lupus-like syndrome diarrhea with liquid preparations that contain sorbitol... 

Drug fever, lupus-like syndrome I Serious Reactions... 

Adverse effects include nausea, vomiting, tachycardia, dizziness, fatigue, weakness, palpitations, headache, paresthesia, tremor, constipation, anxiety, nasal congestion, lupus like syndrome and sleep disturbances. 

Other reactions include a lupus-like syndrome (again, primarily associated with iproniazid), rash, and total suppression of REM sleep. 

Hydralazine Causes nitric oxide release Vasodilation reduce vascular resistance arterioles more sensitive than veins reflex tachycardia Hypertension minoxidil also used to treat hair loss Oral Toxicity Angina, tachycardia Hydralazine Lupus-like syndrome... 

A delayed serum sickness-like reaction may occur 1-2 weeks after anti-TNF therapy in 1% of patients. These reactions consist of myalgia, arthralgia, jaw tightness, fever, rash, urticaria, and edema and usually require discontinuation of that agent. Positive antinuclear antibodies and anti-double-stranded DNA develop in a small number of patients. Development of a lupus-like syndrome is rare and resolves after discontinuation of the drug. 

Antithyroid drugs, especially propylthiouracil, can be associated with the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis, often manifesting as renal disease. Atypical presentations, with pulmonary capillaritis (58) and lupus-like syndrome (59), have been described in individual cases. Furthermore, two cases of vasculitis have been associated with carbimazole, one presenting with eosinophilic granulomatous vasculitis localized to the stomach (60) and another with p-ANCA positive vasculitis causing simultaneous acute renal insufficiency and massive pulmonary hemorrhage (61). 

Ozkan HA, Ozkalemkas F, Ah R, Ozkocaman V, Ozcelik T. Propylthiouracil-induced lupus-like syndrome successful management with oral corticosteroids. Thyroid 2005 15(10) 1203 1. 

A patient developed atorvastatin-induced severe autoimmune hepatitis and a lupus-like syndrome. Although the drug was immediately withdrawn, the disease persisted and deteriorated to a fulminant form with acute hepatic failure. There was no response to conventional immunosuppression with glucocorticoids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery. The patient had the HLA haplotypcs DR3 and DR4, which are well-known genetic factors associated with autoimmune diseases. 

This case is the first report of drug-induced lupus-like syndrome concomitant with severe autoimmune hepatitis in a genetically predisposed patient (23). 

Graziadei IW. Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. Lupus 2003 12 409-12. 

Sridhar MK, Abdulla A. Fatal lupus-like syndrome and ARDS induced by fluvastatin. Lancet 1998 352(9122) 114. 

Statin-induced lupus-like syndrome is characterized by a long delay between the start of therapy and the skin eruption. Antinuclear antibodies can persist for many months after drug withdrawal. The causal relation may be therefore difficult to establish, and probably many cases are unrecognized. Early diagnosis may avoid unnecessary immunosuppressive therapy. 

Lupus-like syndrome has been associated with simvastatin, with antibodies to double-stranded DNA in the serum (34). 

Noel B, Panizzon RG. Lupus-like syndrome associated with statin therapy. Dermatology 2004 208(3) 276-7. 

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