-corticoid

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/21 14:40:49」(JST)

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Corticosterone

Corticosteroids are a class of chemicals that includes steroid hormones naturally produced in the adrenal cortex of vertebrates and analogues of these hormones that are synthesized in laboratories. Corticosteroids are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.^[1]
Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney.

Some common natural hormones are corticosterone (C
21H
30O
4), cortisone (C
21H
28O
5, 17-hydroxy-11-dehydrocorticosterone) and aldosterone.

1 Biosynthesis
2 Classification
- 2.1 By chemical structure
  - 2.1.1 Group A — Hydrocortisone type
  - 2.1.2 Group B — Acetonides (and related substances)
  - 2.1.3 Group C — Betamethasone type
  - 2.1.4 Group D — Esters
    - 2.1.4.1 Group D₁ — Halogenated (less labile)
    - 2.1.4.2 Group D₂ — Labile prodrug esters
- 2.2 By route of administration
  - 2.2.1 Topical steroids
  - 2.2.2 Inhaled steroids
  - 2.2.3 Oral forms
  - 2.2.4 Systemic forms
3 Uses of corticosteroids
4 History
5 Side-effects
6 Safety
7 See also
8 References

Biosynthesis[edit]

Corticosteroid biosynthetic pathway in rat

The corticosteroids are synthesized from cholesterol within the adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase).

Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions), but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona fasciculata and zona glomerulosa.

Classification[edit]

By chemical structure[edit]

In general, corticosteroids are grouped into four classes, based on chemical structure. Allergic reactions to one member of a class typically indicate an intolerance of all members of the class. This is known as the "Coopman classification",^[2] after S. Coopman, who defined this classification in 1989.^[3]

The highlighted steroids are often used in the screening of allergies to topical steroids.^[4]

Group A — Hydrocortisone type[edit]

Hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, and prednisone (Short- to medium-acting glucocorticoids).

Group B — Acetonides (and related substances)[edit]

Triamcinolone acetonide, triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, and halcinonide.

Group C — Betamethasone type[edit]

Betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, and fluocortolone.

Group D — Esters[edit]

Group D₁ — Halogenated (less labile)[edit]

Hydrocortisone-17-valerate, halometasone, alclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone-17-butyrate, clobetasol-17-propionate, fluocortolone caproate, fluocortolone pivalate, and fluprednidene acetate.

Group D₂ — Labile prodrug esters[edit]

Hydrocortisone-17-butyrate, hydrocortisone-17-aceponate, hydrocortisone-17-buteprate, and prednicarbate.

By route of administration[edit]

Topical steroids[edit]

Main article: Topical steroid

For use topically on the skin, eye, and mucous membranes.

Topical corticosteroids are divided in potency classes I to IV,

Inhaled steroids[edit]

for use to treat the nasal mucosa, sinuses, bronchii, and lungs.^[5] This group includes:

Flunisolide^[6]
Fluticasone propionate^[6]
Triamcinolone acetonide^[6]
Beclomethasone dipropionate^[6]
Budesonide^[6]

There is also a combination preparation (trade name Advair), containing fluticasone propionate and salmeterol xinafoate (a long-acting bronchodilator).^[6] It is approved for children over 12 years old.

Oral forms[edit]

Such as prednisone and prednisolone.^[7]

Systemic forms[edit]

Available in injectables for intravenous and parenteral routes.^[7]

Uses of corticosteroids[edit]

Synthetic pharmaceutical drugs with corticosteroid-like effects are used in a variety of conditions, ranging from brain tumors to skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is available for replacement therapy, e.g. in adrenal insufficiency and congenital adrenal hyperplasia.

Synthetic glucocorticoids are used in the treatment of joint pain or inflammation (arthritis), temporal arteritis, dermatitis, allergic reactions, asthma, hepatitis, systemic lupus erythematosus, inflammatory bowel disease (ulcerative colitis and Crohn's disease), sarcoidosis and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency.^[8] Topical formulations are also available for the skin, eyes (uveitis), lungs (asthma), nose (rhinitis), and bowels. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists (e.g. ondansetron).

Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side-effects are hypertension (abnormally high blood pressure), hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood) without causing peripheral edema, metabolic alkalosis and connective tissue weakness.^[9] There may also be impaired wound healing or ulcer formation because of the immunosuppressive effects.

Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing central serous retinopathy (CSR, also known as central serous chorioretinopathy, CSC). A variety of steroid medications, from anti-allergy nasal sprays (Nasonex, Flonase) to topical skin creams, to eye drops (Tobradex), to prednisone have been implicated in the development of CSR.^[10]^[11]

Corticosteroids have been widely used in treating people with traumatic brain injury.^[12] A systematic review identified 20 randomised controlled trials and included 12,303 participants, then compared patients who received corticosteroids with patients who received no treatment. The authors recommended people with traumatic head injury should not be routinely treated with corticosteroids.^[13]

History[edit]

First known use was in 1944.^[14] Tadeusz Reichstein together with Edward Calvin Kendall and Philip Showalter Hench were awarded the Nobel Prize for Physiology and Medicine in 1950 for their work on hormones of the adrenal cortex, which culminated in the isolation of cortisone.^[15]

Corticosteroids have been used as drug treatment for some time. Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a complicated 36-step process that started with deoxycholic acid, which was extracted from ox bile.^[16] The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker, at Syntex, discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams. His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception.^[17] In 1952, D.H. Peterson and H.C. Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.^[18] The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $0.46 per gram by 1980. Percy Julian's research also aided progress in the field.^[19] The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.

Side-effects[edit]

Side effects such as cutaneous addiction with the development of uncomfortable and unsightly dermatoses, can occur with just one 15 g tube of moderate steroid over a period of one year.^[20]

Use of corticosteroids has numerous side-effects, some of which may be severe:

Neuropsychiatric: steroid psychosis,^[21] and anxiety,^[22] depression. Therapeutic doses may cause a feeling of inappropriate well-being ("steroid euphoria").^[23] The neuropsychiatric effects are partly mediated by sensitization of the body to the actions of adrenaline. Therapeutically, the bulk of corticosteroid dose is given in the morning to mimic the body's diurnal rhythm; if given at night, the feeling of being energized will interfere with sleep. An extensive review is provided by Flores and Gumina.^[24]
Cardiovascular: Corticosteroids can cause sodium retention through a direct action on the kidney, in a manner analogous to the mineralocorticoid aldosterone. This can result in fluid retention and hypertension.
Metabolic: Corticosteroids cause a movement of body fat to the face and torso, resulting respectively in "moon face" and "buffalo hump". and away from the limbs. Due to the diversion of amino-acids to glucose, they are considered anti-anabolic, and long term therapy can cause muscle wasting ^[25]
Endocrine: By increasing the production of glucose from amin-acid breakdown and opposing the action of insulin, corticosteroids can cause hyperglycemia,^[22] insulin resistance and diabetes mellitus,.^[22] By inhibition of the action of sex steroids, they can cause erectile dysfunction, hypogonadism and amenorrhoea.
Skeletal: Steroid-induced osteoporosis imay be a side-effect of long-term corticosteroid use. While cases of colitis have been reported, corticosteroids are therapeutically employed when the colitis has an auto-immune nature, e.g., ulcerative colitis and Crohn's disease.
Gastro-intestinal: While the evidence for corticosteroids causing peptic ulceration is relatively poor except for high doses taken for over a month,^[26] the majority of doctors as of 2010^[update] still believe this is the case, and would consider protective prophylactic measures.^[27]
Eyes: chronic use may predispose to cataract and retinopathy.
Vulnerability to infection: By suppressing immune reactions (which is one of their main reasons for their use in allergies), steroids may cause infections to flare up, notability candidiasis^[28]
Pregnancy: Corticosteroids have a low but significant teratogenic effect, causing a few birth defects per 1,000 pregnant women treated. Corticosteroids are therefore contraindicated in pregnancy.^[29]

Safety[edit]

Corticosteroids were voted Allergen of the Year in 2005 by the American Contact Dermatitis Society.^[30]

References[edit]

^ Joseph P. Edardes. "Steroids and Warfarin Therapy". Coumarin Anticoagulant Research Progress. Nova Publishers, 2008. p. 18.
^ Rietschel, Robert L. (2007). Fisher's Contact Dermatitis, 6/e. Hamilton, Ont: BC Decker Inc. p. 256. ISBN 1-55009-378-9.
^ Coopman S, Degreef H, Dooms-Goossens A (July 1989). "Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids". Br. J. Dermatol. 121 (1): 27–34. doi:10.1111/j.1365-2133.1989.tb01396.x. PMID 2757954.
^ Wolverton, SE (2001). Comprehensive Dermatologic Drug Therapy. WB Saunders. p. 562.
^ "Asthma Steroids: Inhaled Steroids, Side Effects, Benefits, and More". Webmd.com. Retrieved 2012-11-30.
^ ^a ^b ^c ^d ^e ^f Frieden, Thomas R. (03/2004). "Inhaled Corticosteroids — Long-Term Control Asthma medicine". New York City Asthma Initiative.
^ ^a ^b "Systemic steroids (corticosteroids). DermNet NZ". . DermNet NZ. 2012-05-19. Retrieved 2012-11-30.
^ Higashi AS, Zhu S, Stafford RS, Alexander GC. "National trends in outpatient asthma treatment, 1997-2009". Journal of General Internal Medicine 26: 1465–1470. PMID 21769507.
^ Werner R (2005). A massage therapist's guide to Pathology (3rd ed.). Pennsylvania: Lippincott Williams & Wilkins.
^ Carvalho-Recchia, CA; Yannuzzi, LA; Negrão, S; Spaide, RF; Freund, KB; Rodriguez-Coleman, H; Lenharo, M; Iida, T (2002). "Corticosteroids and central serous chorioretinopathy". Ophthalmology 109 (10): 1834–7. doi:10.1016/S0161-6420(02)01117-X. PMID 12359603.
^ "The New York Times :: A Breathing Technique Offers Help for People With Asthma". buteykola.com. Retrieved 2012-11-30.
^ Alderson P, Roberts I. "Plain Language Summary". Corticosteroids for acute traumatic brain injury. The Cochrane Collaboration. p. 2.
^ Alderson, P.; Roberts, I. (2005). "Corticosteroids for acute traumatic brain injury". In Alderson, Phil. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD000196.pub2. edit
^ Webster. "First therapeutic use of Corticosteroid". Retrieved 30 July 2012.
^ http://nobelprize.org/nobel_prizes/medicine/laureates/1950/kendall-lecture.pdf
^ Sarett, Lewis H. (1947). “Process of Treating Pregnene Compounds”, U. S. Patent 2,462,133
^ Marker, Russell E.; Wagner, R. B.; Ulshafer, Paul R.; Wittbecker, Emerson L.; Goldsmith, Dale P. J.; Ruof, Clarence H. (1947). "Steroidal Sapogenins". J. Am. Chem. Soc. 69 (9): 2167–2230. doi:10.1021/ja01201a032. PMID 20262743.
^ Peterson D.H., Murray, H.C. (1952). "Microbiological Oxygenation of Steroids at Carbon 11". J. Am. Chem. Soc. 74 (7): 1871–2. doi:10.1021/ja01127a531.
^ Julian, Percy L., Cole, John Wayne, Meyer, Edwin W., and Karpel, William J. (1956) “Preparation of Cortisone”. U. S. Patent 2,752,339
^ Kenneth P Fowler and David J Elpern (2001). ""Tortured tube" sign". Western Journal of Medicine 174 (6): 383–384. doi:10.1136/ewjm.174.6.383. PMC 1071421. PMID 11380999.
^ Hall, Richard. "Psychiatric Adverse Drug Reactions: Steroid Psychosis". Director of Research Monarch Health Corporation Marblehead, Massachusetts.
^ ^a ^b ^c Korte SM (2001). "Corticosteroids in relation to fear, anxiety and psychopathology". Neurosci Biobehav Rev 25 (2): 117–42. doi:10.1016/S0149-7634(01)00002-1. PMID 11323078.
^ C R Swinburn, J M Wakefield, S P Newman, and P W Jones Evidence of prednisolone induced mood change ('steroid euphoria') in patients with chronic obstructive airways disease. Br J Clin Pharmacol. 1988 December; 26(6): 709–713. URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386585/
^ Benjamin H. Flores and Heather Kenna Gumina. The Neuropsychiatric Sequelae of Steroid Treatment. URL: http://www.dianafoundation.com/articles/df_04_article_01_steroids_pg01.html
^ Per-Olof Hasselgren, Nima Alamdari, Zaira Aversa, Patricia Gonnella, Ira J Smith, and Steven Tizio. CORTICOSTEROIDS AND MUSCLE WASTING ROLE OF TRANSCRIPTION FACTORS, NUCLEAR COFACTORS, AND HYPERACETYLATION. Curr Opin Clin Nutr Metab Care. 2010 July; 13(4): 423–428. URL: http://ncbi.nlm.nih.gov/pmc/PMC2911625http://ncbi.nlm.nih.gov/pmc/PMC2911625
^ Pecora PG, Kaplan B (1996). "Corticosteroids and ulcers: is there an association?". Ann Pharmacother 30 (7–8): 870–2. PMID 8826575.
^ Martínek J, Hlavova K, Zavada F, et al. (June 2010). ""A surviving myth" — corticosteroids are still considered ulcerogenic by a majority of physicians". Scand J Gastroenterol 45 (10): 1156–61. doi:10.3109/00365521.2010.497935. PMID 20569095.
^ Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T, Kohno S. Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone.Ann Allergy Asthma Immunol. 2003 Jun;90(6):646-51. http://www.ncbi.nlm.nih.gov/pubmed/12839324
^ Shepard, TH.; Brent, RL.; Friedman, JM.; Jones, KL.; Miller, RK.; Moore, CA.; Polifka, JE. (April 2002). "Update on new developments in the study of human teratogens". Teratology 65 (4): 153–61. doi:10.1002/tera.10032. PMID 11948561.
^ "Contact Allergen of the Year: Corticosteroids: Introduction". Medscape.com. 2005-06-13. Retrieved 2012-11-30.

UpToDate Contents

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1. ステロイドの全身投与の主な副作用 major side effects of systemic glucocorticoids
2. ステロイドの薬理学的使用 pharmacologic use of glucocorticoids
3. ステロイド用量の決定因子 determinants of glucocorticoid dosing
4. ステロイドの中断 glucocorticoid withdrawal
5. 免疫系に対するステロイドの影響 glucocorticoid effects on the immune system

English Journal

Spironolactone, not furosemide, improved insulin resistance in patients with chronic heart failure.

Ogino K1, Kinugasa Y2, Kato M2, Yamamoto K2, Hisatome I3, Anker SD4, Doehner W5.Author information 1Division of Clinical Laboratory, Tottori University Hospital, Yonago, Japan. Electronic address: ko-36@umin.ac.jp.2Department of Cardiovascular Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.3Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medicine, Yonago, Japan.4Division of Applied Cachexia Research, Department of Cardiology, Campus Virchow-Klinikum Charite Universitätsmedizin, Berlin, Germany.5Center for Stroke Research Berlin, Charite Universitätsmedizin, Berlin, Germany.AbstractBACKGROUND/OBJECTIVES: Insulin resistance plays an important role in the pathophysiology in chronic heart failure (CHF). Diuretics generally have harmful effects on glucose metabolism, however, the effect of mineral corticoid receptor blockers on insulin resistance in CHF is unclear. This study aimed to evaluate the effects of the aldosterone blocker spironolactone, in comparison with furosemide, on insulin resistance in CHF patients.
International journal of cardiology.Int J Cardiol.2014 Feb 15;171(3):398-403. doi: 10.1016/j.ijcard.2013.12.039. Epub 2013 Dec 27.
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Prednisone in lupus nephritis: how much is enough?

Ruiz-Irastorza G, Danza A, Perales I, Villar I, Garcia M, Delgado S, Khamashta M.Author information Autoimmune Diseases Research Unit, Department of Internal Medicine, Biocruces Health Research Institute, Hospital Universitario Cruces, Spain; University of the Basque Country, Bizkaia, The Basque Country, Spain. Electronic address: r.irastorza@euskaltel.net.AbstractOBJECTIVE: To assess the effectiveness and safety of a protocol using medium doses of prednisone to treat lupus nephritis.
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PMID 24189280

Long-term follow-up of a randomized trial on 118 patients with polyarteritis nodosa or microscopic polyangiitis without poor-prognosis factors.

Samson M, Puéchal X, Devilliers H, Ribi C, Cohen P, Bienvenu B, Ruivard M, Terrier B, Pagnoux C, Mouthon L, Guillevin L; French Vasculitis Study Group (FVSG).Collaborators (77)Alcalay M, Arnal C, Battesti JP, Bergère A, Bernardeau C, Boullanger N, Sao AB, Buzon JJ, Cabane J, Cacoub P, Cantagrel A, Cevallos R, Costedoat JC, Créange A, Dadoniene J, de Faucal P, Defuentes G, de Seze J, Delaunay C, Dubertret L, Dubois A, Duhamel E, Neau D, Estève E, Fior R, Foullon P, TsouriaGaida, Galperine T, Garcin JM, Gil H, Gilson B, Girard T, Godeau B, Godmer P, Gueit I, Hamidou M, Israel-Biet D, Labussière AS, Landron C, Lanoux P, Le Berruyer PY, Lhote F, Lidove O, Loustaud-Ratti V, Maillard H, Mejjad O, Miossec P, Paris JF, Penalba C, Pertuiset E, Philippe JM, Ponge T, Quéré I, Randrianjohany A, Rankin E, Roux M, Saraux JL, Schaeffer A, Schmidt C, Schneebeli S, Seigneuric C, Smail A, Sparsa A, Stirnemann J, Swiader L, Taillandier JP, Thévenot C, Tiev KP, Tolédano C, Velmans N, Viallard JF, Vidal E, Wahl D, Wattiaux MJ, Witte A, Ziza JM, Zoulim A.
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Japanese Journal

Corticoid Therapy for Overlapping Syndromes in an HIV-positive Patient

Internal Medicine 54(2), 223-230, 2015
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3-Monoglucuronyl Glycyrrhretinic Acid Is a Possible Marker Compound Related to Licorice-Induced Pseudoaldosteronism

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Molecular cloning and characterization of the corticoid receptors from the American alligator

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NAID 120005228364

Related Pictures

★リンクテーブル★

リンク元	「100Cases 33」「コルチコイド」「adrenal cortex hormone」
拡張検索	「mineral corticoid」「glucocorticoid resistance」「glucocorticoid」
関連記事	「cortico」

「100Cases 33」

　　[★]

☆case33　頭痛と混乱

■glossary

accompany

vt.

(人)と同行する、(人)に随行する。(もの)に付随する。～と同時に起こる。～に加える(添える、同封する)(with)

slurred n. 不明瞭

強直間代痙攣 tonic-clonic convulsion

　意識消失とともに全身の随意筋に強直痙攣が生じ(強直痙攣期tonic convulsion)、次いで全身の筋の強直と弛緩とが律動的に繰り返される時期(間代痙攣期clonic convulsion)を経て、発作後もうろう状態を呈する一連の発作。

■症例

28歳、女性　黒人　南アフリカ　手術室看護師　ロンドン住在

主訴：頭痛と混乱

現病歴：過去3週間で頭痛が続いており、ひどくなってきた。現在も頭痛が持続しており、頭全体が痛い。友人曰く「過去六ヶ月で体重が10kg減っていて、最近、混乱してきたようだ」。発話は不明瞭。救急室にいる間に強直間代痙攣を起こした。

・診察 examination

やせている。55kg。38.5℃。口腔カンジダ症(oral candidiasis)。リンパ節腫脹無し。心血管、呼吸器系、消化器系正常。痙攣前における神経検査では時間、場所、人の見当識無し。神経局所症状無し(no focal neurological sign)。眼底両側に乳頭浮腫有り。

・検査 investigation

血算：白血球増多

血液生化学：ナトリウム低下

CT：供覧

■キーワード＆着目するポイント

・口腔カンジダ症(oral candidiasis)

・頭痛、精神症状、強直間代痙攣

・眼底両側に乳頭浮腫

・CT 所見

・低ナトリウム血症は二次的なもの

■アプローチ

・口腔カンジダ症(oral candidiasis)　→　細胞免疫低下状態(DM、免疫抑制、AIDSなど) or 常在細菌叢の攪乱(長期の抗菌薬の使用)

　・The occurrence of thrush in a young, otherwise healthy-appearing person should prompt an investigation for underlying HIV infection.(HIM.1254)

　・More commonly, thrush is seen as a nonspecific manifestation of severe debilitating illness.(HIM.1254)

・精神症状、強直間代痙攣　→　一次的、あるいは二次的な脳の疾患がありそう

・頭痛　→　漠然としていて絞れないが、他の症状からして機能性頭痛ではなく症候性頭痛っぽい。

・眼底両側に乳頭浮腫　→　脳圧亢進の徴候　→　原因は・・・脳腫瘍、ことにテント下腫瘍と側頭葉の腫瘍、クモ膜下出血、脳水腫など、そのほか、眼窩内病変、低眼圧などの局所的要因、悪性高血圧、血液疾患、大量出血、肺気腫などの全身的要因 (vindicate本のp342も参考になる)

　・頭痛と脳圧亢進　→　頭蓋内圧占拠性病変、脳炎(IMD.274)

・CT 所見　→　ringformの病変、脳浮腫、脳圧亢進

・低ナトリウム血症　→　脳ヘルニアに続発して起こることがあるらしい。実際には下垂体にトキソプラズマによる病変が形成されることにより起こりうる。

・そのほか出身地、体重減少もHIVを疑わせる点

パターン認識でHIV + 精神症状 + てんかん発作(強直間代痙攣) + 脳圧亢進 + CT 所見 = 一番ありそうなのはToxoplasma gondiiによるトキソプラズマ脳症 cerebral toxoplasosis (トキソプラズマ脳炎 toxoplasmic encephalitis)

■Toxoplasma gondii

　原虫　胞子原虫類

(感染予防学 080521のプリント、CASES p,92、HIM p.1305-)

・疫学：西洋では30-80%の成人がトキソプラズマの感染の既往がある・・・うぇ(CASES)。日本では10%前後(Wikipedia)。

・生活環

　・終宿主：ネコ：ネコの小腸上皮細胞で有性・無性生殖　糞便にオーシストの排泄

　・中間宿主：ヒト.ブタを含むほ乳類と鳥類：無性生殖で増殖、シストの形成

　　　急性期の増殖盛んな急増虫体 tachyzoiteとシスト内の緩増虫体 bradyzoite

・病原、病因 phathogenesis

　・緩増虫体(bradyzoite)、接合子嚢(oocyst)

・感染経路

　1. オーシストの経口摂取

　2. 中間宿主の生肉中のシストの経口摂取

　3. 初感染妊婦からの経胎盤感染。既感染なら胎盤感染しないらしい(HIM.1306)

　(4)移植臓器、輸血。確率は低い(at low rate)(HIM.1306)

・病態

　1. 先天性トキソプラズマ症　congenital toxoplasmosis

　　　①網脈絡膜炎、 ②水頭症、 ③脳内石灰化、 ④精神・運動障害

　2. 後天性トキソプラズマ症　acquired toxoplasmosis

　　(1) 健常者

　　　・多くは不顕性感染。発熱、リンパ節腫脹、皮疹(rash)

　　　・(少数例)筋肉痛、暈疼痛、腹痛、斑状丘疹状皮疹(maculopapular rash)、脳脊髄炎、混乱(HIM.1308)

　　　・(まれ)肺炎、心筋炎、脳症、心膜炎、多発筋炎

　　　・網膜、脈絡叢に瘢痕や、脳に小さい炎症性の病変を残すことあり(CASES)。

　　　・急性感染の症状は数週間で消失　筋肉や中枢神経系に緩増虫体が残存

　　(2)HIV 感染者、臓器移植例、がん化学療法例

　　　シスト内緩増虫体→急増虫体→播種性の多臓器感染

　　　AIDSでは、トキソプラズマ性脳炎が指標疾患 AIDS-defineing illness(CASES)

・治療

　(日本)アセチルスピラマイシン、ファンシダール(感染予防学 080521)

■トキソプラズマ脳炎 toxoplasmic encephalitis、トキソプラズマ脳症 cerebral toxoplasosis

・症状

　発熱、頭痛、混乱ｍ、痙攣、認知の障害、局所神経徴候(不全片麻痺、歯垢、脳神経損傷、視野欠損、感覚喪失)(CASES)

・画像検査

　(CT,MRI)多発性、両側性、ring-enhancing lesion、特に灰白質-白質境界、大脳基底核、脳幹、小脳が冒されやすい(CASES)

・鑑別診断(臨床症状・画像診断の所見で)

　リンパ腫、結核、転移性脳腫瘍(CASES)

・病歴と画像所見からの鑑別診断

　リンパ腫、結核、転移性腫瘍

？

このCTがcerebral toxoplasmosisに特徴的かは不明

□最後に残る疑問

　AIDSでWBC(leukocyte)の数はどうなるんだろう？？？AIDSの初診患者ではWBCが低い人が多いらしいし()、HIVはCD4+ T cellとmacrophageに感染して殺すから、これによってB cellは減るだろうし、CD8+ T cellも若干減少するだろうからWBCは減るんじゃないか？！好中球はAIDSとは関係ない？好中球は他の感染症に反応性に増加している？ちなみに、好酸球は寄生虫(原虫)の感染のために増える傾向にあるらしい(HIMのどこか)。

葉酸拮抗剤である。

サルファ剤と併用され、抗トキソプラズマ薬、抗ニューモシチス・カリニ薬として相乗的に働く。

ST 合剤

SMX-TMP

スルファメトキサゾール・トリメトプリム合剤 sulfamethoxazole and trimethoprim mixture

□AIDSの定義(http://en.wikipedia.org/wiki/CDC_Classification_System_for_HIV_Infection_in_Adults_and_Adolescents)