Gene/Protein Disease Symptom Drug Enzyme Compound
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The antimalarials, mainly chloroquine and hydroxychloroquine, derive from the quinoleine core of quinine. Their initial therapeutic indication was the treatment of malaria attacks but, because of anti-inflammatory and immuno-modulatory activities, they have been since used to treat many other pathologies, in particular dermatological ones. For some of these pathologies, lupus or porphyria cutanea tarda for example, the use of these molecules is based on obvious scientific evidence. For other pathologies (cutaneous sarcoidosis, polymyositis, polymorphous light eruption...), the data on the medical literature corroborating the daily clinical practice are extremely poor. Their toxicity is limited. Their most common toxic effects are gastrointestinal (mild nausea or diarrhea) or mucocutaneous (reversible skin or mucosal pigmentation). Their most serious and dreaded side effect, retinopathy, can be largely prevented by using amounts of APS adapted to the weight of the patients. The recommended "safe" daily dose for hydroxychloroquine is 6.5 mg per kilogramme of body weight and for chloroquine 4 mg per kilogramme of body weight. However, at 6- to 12 months intervals, follow-up eye examinations should be performed.
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PMID:[Synthetic antimalarials]. 1623 Sep 16

Hydralazine was one of the first orally active antihypertensive drugs developed. Currently, it is used principally to treat pregnancy-associated hypertension. Hydralazine causes two types of side effects. The first type is an extension of the pharmacologic effect of the drug and includes headache, nausea, flushing, hypotension, palpitation, tachycardia, dizziness, and salt retention. The second type of side effects is caused by immunologic reactions, of which the drug-induced lupus-like syndrome is the most common, and provides clues to underscoring hydralazine's DNA demethylating property in connection with studies demonstrating the participation of DNA methylation disorders in immune diseases. Abnormalities in DNA methylation have long been associated with cancer. Despite the fact that malignant tumors show global DNA hypomethylation, regional hypermethylation as a means to silence tumor suppressor gene expression has attracted the greatest attention. Reversibility of methylation-induced gene silencing by pharmacologic means, which in turns leads to antitumor effects in experimental and clinical scenarios, has directed efforts toward developing clinically useful demethylating agents. Among these, the most widely used comprise the nucleosides 5-azacytidine and 2'deoxy-5-azacytidine; however, these agents, like current cytotoxic chemotherapy, causes myelosuppression among other side effects that could limit exploitation of their demethylating properties. Among non-nucleoside DNA demethylating drugs currently under development, the oral drug hydralazine possess the ability to reactivate tumor suppressor gene expression, which is silenced by promoter hypermethylation in vitro and in vivo. Decades of extensive hydralazine use for hypertensive disorders that demonstrated hydralazine's clinical safety and tolerability supported its testing in a phase I trial in patients with cancer, confirming its DNA demethylating activity. Hydralazine is currently being evaluated, along with histone deacetylase inhibitors either alone or as adjuncts to chemotherapy and radiation, for hematologic and solid tumors in phase II studies.
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PMID:Hydralazine target: from blood vessels to the epigenome. 1650

This article describes a 57-year-old woman with SLE and positive antiphospholipid and lupus anticoagulant antibodies (Ig type M) who developed an acute Addisonian crisis due to bilateral adrenal haemorrhage. It is important to recognise that bilateral adrenal haemorrhage can be part of the thrombo-embolic complications that are seen in both the primary and the secondary APS. Since there have been a number of similar cases, we suggest that APS with adrenal haemorrhage should be taken into consideration in SLE patients with abdominal pain, fever, nausea, hypotension and hyponatremia.
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PMID:[Acute Addisonian crisis in a patient with systemic lupus erythematosus and secondary antiphospholipid syndrome]. 1759 92

Listeria monocytogenes (LM) is one of the rare microorganisms causing peritonitis in peritoneal dialysis (PD) patients. We report a sporadic case of peritonitis caused by LM in a young female PD patient with lupus receiving corticosteroid therapy, who presented with abdominal pain, cloudy PD effluent, nausea, and conjunctivitis. The effluent showed a high PD effluent white cell count and monocytosis, and gram staining showed gram-positive bacilli in single or short chains and PD effluent culture grew LM. She was treated successfully with beta lactum antibiotics. LM peritonitis should be suspected if a patient presents with gram-positive bacilli and monocytosis in dialysis effluent.
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PMID:Listeria monocytogenes peritonitis in a patient on peritoneal dialysis: a case report and review of the literature. 1856 14

The patient was a 74-year-old woman. As the history of the present illness, Raynaud's phenomenon appeared in 1998, antinuclear antibody positivity was detected in 2002, and she visited our department for the first time. Leukopenia and positivity for anti-DNA and anti-RNP antibodies were present, but active lesions were not, and thus, course observation was selected. Pollakiuria and a sensation of residual urine appeared in February 2005, diarrhea and nausea developed in November, and she was admitted to our hospital. Abdominal CT detected bilateral hydronephrosis, marked hydroureter, and hypertrophy of the urinary bladder wall, cystoscopy detected trabeculation, and features of interstitial cystitis were noted on biopsy. Edematous colon mucosa was noted on lower endoscopy, submucosal inflammatory cell infiltration on biopsy, and IgG deposition in the small vascular wall on immunostaining. Systemic lupus erythematosus (SLE) that developed as lupus cystitis was diagnosed. The clinical findings were improved by 50 mg of prednisolone. Although she developed lupus cystitis at an elderly age of 74 years, IgG deposition in the small vascular wall was detected by immunostaining of the intestinal mucosa. It is a valuable case proved that causative disease of a digestive tract symptom was enterocolitis through an immune complex as autoimmune reaction by SLE immunohistologically. There are 46 cases of lupus cystitis in Japan by 2007 since Kato reported lupus cystitis in 1985. We summarize clinical features of 46 cases and discuss difference with this case.
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PMID:[A case of lupus cystitis in a 74-year-old woman]. 1858 30

Lupus cystitis is a rare manifestation in systemic lupus erythematosus (SLE); it usually occurs in association with gastrointestinal manifestations. We report two cases of lupus cystitis without bladder irritation symptoms. Both cases developed severe abdominal pain, nausea, and diarrhea and showed no bladder irritation symptoms. The diagnosis of lupus cystitis was made by abdominal ultrasonography and bladder biopsy. The patients were treated with intravenous methylprednisolone pulse therapy followed by oral prednisolone. Their symptoms were ameliorated, and hydroureteronephrosis improved. Thus, when a patient with SLE shows gastrointestinal symptoms, further examinations are required to determine whether the patient has lupus cystitis.
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PMID:Two cases of lupus cystitis with no bladder irritation symptoms. 1870 58

We describe a case of simultaneous severe lupus enteritis and lupus cystitis in a 38-year-old female with a 21-year history of systemic lupus erythematosus (SLE). The patient presented with acute abdominal pain, decreased urinary output, associated low-grade fever, nausea, and diarrhea. She had serologic evidence of an SLE flare with acute renal insufficiency. Computed tomography examination revealed dramatic edema of the large- and small-bowel walls with no evidence of bowel loop dilatation or pneumatosis intestinalis, marked diffuse thickening of the urinary bladder wall, and bilateral hydronephrosis and hydroureter. Lupus enteritis and lupus cystitis were diagnosed and treatment with intravenous corticosteroids led to prompt resolution of the abdominal pain and normalization of renal function. Because infarction of tissue and bowel rupture are potentially fatal complications, it is essential to consider lupus enteritis in SLE patients who present with abdominal pain. This case demonstrates that once lupus enteritis is suspected, coexistent lupus cystitis must also be considered.
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PMID:Recognizing concomitant lupus enteritis and lupus cystitis. 1876 23

To evaluate the efficacy of hydroxychloroquine (HCQ) and quinacrine (Qn) association, at two different dosages, in treatment of lupus skin lesions not responding to HCQ alone. Thirty-four patients, affected by cutaneous and systemic lupus erythematosus, were retrospectively analysed. They were treated by HCQ (5 mg/Kg/qd) and Qn with two regimens: 100 mg/qd (29 cases) and 50 mg/qd (5 cases). Discoid lupus erythematosus (19 cases), acute malar rash (6 cases), chilblain lupus (4 cases) showed a significant improvement with combination therapy (P = 0.009, P = 0.019, and P = 0.04, respectively). Ten patients with subacute cutaneous lupus showed a partial response, whereas lupus profundus didn't improve. The same overall response rate was recorded comparing two Qn regimens, but subjects taking 100 mg/qd improved more rapidly than the others (P = 0.001). Ten patients developed side effects, mainly represented by skin yellowish discolouration. Depression and severe headache with nausea, which were globally recorded in two cases, led to drug withdrawal. One additional case of hepatitis was recorded in a patient with preexisting Hepatitis C virus (HCV) infection. Combination of HCQ and Qn is rapidly effective at 100 mg/qd and well tolerated in the treatment of lupus skin lesions unresponsive to HCQ alone.
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PMID:Treatment of lupus skin involvement with quinacrine and hydroxychloroquine. 1950 70

A 55-year-old man presented to the emergency department with a 12-hour history of severe crampy abdominal pain, nausea, vomiting and obstipation. The patient had a complex medical history, including coronary artery disease, lupus, hypothyroidism, epilepsy, pancreatitis and renal calculi. However, the patient had no history of a hernia or abdominal surgery. Physical examination revealed a temperature of 38.5 degrees C and a soft distended abdomen that was diffusely tender without signs of peritonitis. The rest of the physical examination was unremarkable. Routine laboratory investigations including a complete blood cell count, electrolytes, liver enzymes and amylase were normal, with the exception of a decreased hemoglobin level of 116 g/L. We ordered a plain abdominal radiograph (Fig. 1) and a contrast-enhanced computed tomography (CT) scan of his abdomen. What is your diagnosis?
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PMID:Soft tissue case 61. 1968 May 23

A 52-year-old woman with a 6-year history of systemic lupus erythematosus (SLE) developed acute abdominal pain, nausea, vomiting, and diarrhea accompanied by hypocomplementemia. Herpes simplex virus (HSV) esophagitis and lupus enteritis were diagnosed on the basis of the results of endoscopic and histological examinations and abdominal computed tomography (CT) findings. Treatment with acyclovir followed by high-dose intravenous steroids improved her symptoms. To our knowledge, this is the first case of simultaneous HSV esophagitis and lupus enteritis.
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PMID:Simultaneous herpes simplex virus esophagitis and lupus enteritis in a patient with systemic lupus erythematosus. 1980 50


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