VASCULAR DISEASE AND VASCULITIS

Q.170. What are the clinical manifestations & diagnosis of W.G. and M.P.?

 

Revise please the abbreviation list on:

https://draft.blogger.com/u/0/blog/post/edit/8610857019469578230/4564412989605988372

Vascular diseases and Vasculitis  

 

Q.170. What are the clinical manifestations & diagnosis of W.G. and M.P.?  

A. Pulm. dis.:  All ptns é W.G present é upper airway/pulm. involv. & majority hv both. One 1/3^rd é pulm. involv.: aSmtic. Pulm. involv. also occ. é MPA. The most common manif.:F[hemoptysis, pulm. hge & pleuritis and/or pl. eff.].

Renal dis.: in WG & MPA manf. By [ARF + hematuria, RBCs casts + Prot.]. R. biopsy: segmental NGN. é few or no immune deposits (pauci-immune) on I.F. &  E/M. Crescents: commnly occ. & almost all pauci-immune CGN. ANCA-+ve. (96 %). ANCA- -ve, pauci-immune CGN= Part of this spectrum & hv similar R. biopsy & prognosis, but there’s diff. in C.P., G. involving usually accompied by mononuclear T.I. infiltrates. However, some ptns present é T.I. +/- granuloma in abs. of typical G. les., but later on hs classic pauci-immune NGN.

R.-limited vasculitis: Alth. pauci-immune NGN. typically occ. é affection  of other organs in WG/MPA, some ptns present é R-limited, ANCA-+ve(80 % MPO-ANCA) vasculitis. R.-limited vasc. is considered a part of WG/MPA spectrum. bec.  histp. finding in  kidney are indistinguishble fr. those in WG &MPA, some ptns usally develop extrarenal manif. of WG or MPA . R.-limited vasc. tend to hv more G. sclerosis on R. biopsy thn those é WG,  bec. ptns é R.-limited dis. present later due to abs. of extrarenal manifestation. Limited form é clinical finding isolated to upper resp. or lungs, occ. in 1/4^th  of cases. Alth. many (80%) dev. G.N., there’re incompletly understood phenolltypic diff. in WG. esp, ptns é limited dis. are younger at dis. onset, and more likely to be women. Despite younger at onset, ptns é limited dis. hv  longer dis. dur. thn ptns é sev. dis. & hv greater likelihood of hv. ch.recurr. dis.. It’s also hv  higher prevelence of destructive upper resp. dis. (e.g, saddle-nose), but less likely to be ANCA +ve or hv autoimmune thyroid dis.. Even if G.N. doesn’t occ. in é limited dis., other organs involv. e.g. pulm., cardiac, G.I. & CNS., may be serious & life-threatening

Q.171.What are the most common Sm. of W.G. & M.P.?  

A. The most comm. Sm.:[persistent rhinorrhea, purulent/bldy nasal disch., oral and/or nasal ulcers, polyarthralgias, myalgias, or sinus pain]. Less cmm.: upper airway Sm.:[hoarseness, stridor, earache, conductive & sensorineural hear-ing loss, otorrhea]. Lower resp. Sm. incl. [Cough, dyspnea, hemoptysis (alv. Cpll.  necrotic, or endobronchial dis.) & pleuritic pain]. Sm. cn be ass. é Sn.  of pulm. cons-olidation and/or pl. effusion. Pulm. Sm. é abs. of upper resp. Sm./Sn are unusual.

“Chest x-ray” find., incl. one or more of:         

      Nodules (may cavitate)

      Alveolar opacities

      Pleural opacities

      Diffuse hazy opacities (alv. hge)

      Hilar adenopathy.

Nonsp. C/O [fever, night sweats, anorexia, wt loss & malaise may occ. é upp. or lower airway dis.]. Sns & Sms of other organs, incl.[Ocular inflmm., nosal congestion, joint tenderness and/or effusion & rash]. Skin les. incl.: {palpable purpura, ulcers, vesicles, papules & s.c. nodules.}. Drr. é colorectal ulceration & Central D.I.

Alth. parenchymal lung nodules are well-recognized manf., WG cn rarely pres-ent é tumor-like masses outside the lung. The most common extra thoracic locations were: breast & kidney. Failure to consider vasculitis in D.D. may lead to unnecessary surgery, incl. nephrectomy. D.gx. of sarcoidosis or pulm. T.B. may be made mistakenly also. R. involv.: comm. component of WG/ MPA. Ptns typically present é active ur. sediment (microscopic hematuria é or without RBCs casts) & degree of R.I., incl. RPGN.. Find. are similar in adults & children .

Q.172. How to make a diagnosis for W.G.? 

A. Clinical criteria : In 1990, “American College of Rheumatology” proposed clinical criteria of W.G. , made prior to ANCA era. The four clinical criteria are:

  1 • Nasal or oral inflmm. (painful or painless oral ulcers or purulent/bldy nasal disch.).                             

  2 • Abn. chest radiograph: [nodules, fixed infiltrates, or cavities].

  3 • Abn. urinary sediment [microsc. hematuria with or without RBCs casts].

  4 • Granulomatous inflmm.  on biopsy of an artery or perivascular area.

Wegener granulomas are ch.ch. by  palisaded arrangement.

Two or more of these 4 criteria sensitivity: 88% & specifity: 92% .Thus, abnormal chest radiograph or  granuloma on biopsy are not absolute indication for WG. Dgx. The main path. diff. between WG. & MPA isF[abs. of “granulom.” in MPA.] Some experts consider anyGsignif. upper resp. les. is indicative of WG.

Routine lab.: nonsp.: leukocytosis, thrombocytosis (>400,000/microL), marked icr. in ESR & CRP & normo.normo. anemia. WG D.gx. sugg. fr. [Clinical & lab. find.+ presence of circul. ANCA].

Q.173. What about “tissue diagnosis”?

A. Dgx. of WG shd be confirmed by tissue biopsy at a site of active dis..Biopsy of nasophx. is preferred (relatively noninvasive). However, all path. features may not be seen. Typical finding on upper resp. biopsies:[ac. & ch. inflmm. + granulo-matous features], is consistent but not diagnostic of WG, as vasculitis sn in only one 1/3^rd of cases. If there’s no lesion in upper resp., next step is biopsy of an affected org. e.g.: skin, kidney, or lung. Skin biopsy: leukocytoclastic vasculitis é little or no C. & Ig.(I.F.). Kid. biopsy: typicallyÜ Segmental necrotizing G.N. tht’s us. pauci-immune(I.F. or E/M.).There’s overlap betw. WG & MPA. The main path. diff. is abs. of granuloma in MPA. Ptns é only pauci-immune G.N. in abs. of other organ affection = "renal-limited" vasculitis or idiop. Necrotiz. G.N.. In abs. of R. affection, Dgx. cn be supported by lung biopsy. Typical histopth. finding= [vasculitis+granulom. inflmm.]; sp. stains & cultures should be performed to exclude other granulomata (e.g,T.B.), vasculitis, or necrosis.

Lung biopsy: Open or thoracoscopic. In <10 %, suff-icient tissue for D.gx. cn be obt. by transbronchial biopsy ; however, abs. of granuloma on transbronchial  specimens should not be considered adequate  evid-ence to exclude D.gx. Initiation of thpy without a confirmatory biopsy may be accepted in rare cases, e.g. sev. ill ventilator-dependent  ptn without extrapul-monery affection in whm, lung biopsy may cause signif. morbidity & mortality.

Q.174. How to distinct W.G. from other systemic diseases?

A. Distinction of WG fr. other systemic rhc dis. is a clinical problem, incl. dis. é similar C.P., similar lung and/or R. Sn., and/or +ve ANCA. Vasculitis in MPA is pathologically indistinguishable fr. Churg-Strauss synd.. Asthma & eosino-philia disting. the later fr. MPA. Distinction is often made betw. MPA & classic PAN: vasculitis of medium sized msc. arteries. As its name, MPA occ. é small vessels (arterioles, venules, cpll.); cpll. us. involved in MPA (incl. G. cpll., ie, G.N.), but arterioles may be spared. Small vessels always spared in PAN. Cardinal features of classic PAN:[R. infarcts, R. vasculitis & visceral micro-aneurysms] not found in MPA & there’re diff. in natural history of these dis.. MPA tends to relapse, while PAN does not. ANCA serologies are also useful in DD. Where as 3/4^th of MPA ptns ANCA +ve, classic PAN not ass. é A.B. to either PR3 or MPO.

Anti-G.B.M. A.B. dis., more rare thn ANCA-ass. vasculitis: it cn present é feat-ures of a pulm./R. synd.. Also, cn occ. together; 10-40 % Anti-G. B.M. also form ANCA (mostly MPO rather thn PR3), a minority of whm hv C.P. of systemic vasculitis.

Q.175. What is the initial immunosuppressive therapy in W.G. & M.P.?

A. WG & MPA: systemic vasculitides  ANCA +ve , similar features & outcomes.

WG/MPA therapy hs twoAcomponents: induction of remission & maintenance im/m.. Complete remission (abs. of active dis.)= goal of initial im/m. Cph. initial thpy:[Cph. + steroids .] Øremission in 90% of ptns, é 2-6 m.

Two Cph. Reg.: daily oral & monthly i.v.. Data fr. trials hv shown tht the two reg.sØ remission of active dis. at a similar rate. Daily oral ühs the adv. of Ø  lower rate of relapse & disadv. of Ö more leukopenia & infection. Ptn.  preference may help reg. choice. Close follow-up & monitor for neutropenia us. indicated. For all ptn. é organ- or life-threating dis. & almost all other ptns é WG/MPA, it’s recommended  initial im/m. é combininatio of: {Cph. (either daily oral or monthly i.v.) + steroids}. If oral Cph given, 1.5-2 mg/kg/d.., until stable remission occ..(3-6 m).. If pulse i.v. Cph given, 0.5-1.0 g/m2 b.s.a./m./ 3-6 m, until stable remissionis induced. Cph ttted ptn., WBC closely monitored & Cph. dose adjusted to avoid severe Leukopenia. WBC should remain >3000/microL & absolute neutrophil count >1500/ microL. ☜

Steroids: used é active WG/MPA.: i.v. pulse Mprd. dep. é dis. severity. Necr-otizing/crescentic G.N./sev. resp. dis. pulse Mprd.:7-15 mg/kg, max.(500-1000 mg /d./3d.) foll. by oral pred. é 4^th d.: 1 mg/kg/d. (max. 60-80 mg/d.). If No necrotiz. G.N./ sev. resp. dis. oral pred. rather thn initial pulse i.v. thp.: 1 mg/kg /d. (max. 60-80 mg/d.) begining on day one. Some clinicians prefer pulse Mprd. for 3 d. Oral pred. is continued at initial dose/2-4 w. If improvment occ., dose tapered qslowly, é goal of 20 mg/d. by end of 2 m. & overall steroids course = 6-9 m. Alternated steroidýreg. is NOT recommended. ! !

Q176.Compare oral versus intravenous cyclophosphamide for ANCA-associated vasculitis?

A.The original randomized trial of daily oral vs pulse i.v. Cph  for ANCA-ass. systemic vasculitis (CYCLOPS) study found similar remission rates in ptn. é granulomatosis é polyangiitis or M.P.; i.v. therapy led to † signif. lower cumula-tive dose & less leukopenia. Long-term foll.-up (4.3 y.) of this trial, more ptn.s in i.v. pulse g. hd at least one relapse (40 vs 21%) & greater total No. of relapses (54 vs 21 relapses). Despite higher relapse rate, there ws no diff. betw. the two g.s in No. of deaths, incid. of ESRD, or median s. Cr..  

Q.177.What are the other options in initial immunosuppressive therapy in W.G. & M.P.?

A. Methotrexate: [Mthx + Steroids]: an alternate to Cph. for highly selected ptns é non-organ threat & non-life threating dis.(pulm. nodules or infiltrates with-out resp. compromise), and/or ocular dis.. Mthxý should NOT be given é GFR <50 mL/ min.

Oral Mthx é initial dose of 0.3 mg/kg.(not>15 mg) once/w., with incr. of 2.5 mg/ w/max. 25 mg once/wk. Since Mthx is an analogue of folic a. competitive inhibit binding of dihydrofolic a. (FH2) to enz. dihydrofolate reductase (DHFR), folic a. (1-2 mg/d.) or folinic a. (2.5-5 mg/w.,24 h. after Mthx) given to dcr. toxicity.

Pph: Adding of Pph to Cph. & G.corticoids enhance recovery of R. func.. Pph for WG/MPA who hv anti-GBM A.B. as well as ANCA; for ptns é sev. pulm Hge on presentation or é sev. pulm. hge despite high-dose steroids & Cph.; & for sev. R. dysf. at presentation, as def. by s.cr.>5.7 mg/dL (500 micromol/L) and/or DX dependence. Advanced R.I. 7 sessions of Pph/2 w.(60 mL/kg/sess.), wch’s prolonged é anti-GBM dis.. Ptns who hv hd recent R. biopsy or pulm. Hge, 1-2 L. of FFP substituted for alb. é end of the procedure to reverse Pph-induced coagulation f. depletion. If No evid. of hge or No risk for bleeding albumin be used as replacement fluid. Ptns é sev. infc. dur. Pph single inf. of i.v. I.G.(100-400 mg/kg) given to partially replenish A.B. levels. P. carinii (jirovecii) pneumonia (PCP) & other opportunestic infc. fatal complic. of im/m. therapy: Estimated incid.: 6 %. So, start: TMP-SMX  1 D.S t./d.

Q.178. How to start maintenance immunosuppressive (Maint) therapy in W.G. & M.P.?

A. WG & MPA ttt. us. begins é Cph. & steroid to induce remission, Cph. then discontinued 1-2 m. after complete remission (us. occ. é 3-6 m.), then start:

Maintenance: shd not be started untilGWBCs.>4000 cells/microL & absolute neutrophil c.>1500 cells/microL. If these criteria met, maintenance can be begun é days after stop of oral Cph & 2-4 w. after last monthly dose of i.v. Cph F(time of leukocyte nadir).

Initiation of Maint thpy é either Mthx. or Aza. to sustain remission is sugg-ested. These drugs are preferred üto long-term Cph., which’s ass. é significant toxicity. Aza. rather thn Mthx. is preferred for initial maintenance if GFR<50 mL/min, dose:2 mg /kg/d. initially & dcr. to 1.5 mg/kg/d. at one y. fr. time of start of induction. Mthx reg. consists of initial dose of 0.3 mg/kg once/w. (max. 15 mg) tht’s incr. by 2.5 mg / w., max. 25 mg once/w.. As Mthx is an analogue of folic a. tht cn competitively inhibit binding of dihydrofolic a. (FH2) to enzyme dihydrofolate reductase (DHFR), folic a.(1-2 mg/d.) or folinic a. (2.5-5 mg/w., 24 h. after Mthx) shd be given to potential toxicity. Maint im/m. thpy. shd be continued 12-18 m.. Longer term or indefinite Maint thpy. may be needed é multiple relapses. Concurrent steroid (prdn): lowest dose required for control of extra-R. Sm.. Ptns remaining aSmc can be slowlyqtapered off steroid therapy.

Q.179. How to deal with Cph-resistant W.G. & M.P.?    Ð

A. Definition: {one or both of the foll. despite therapy for at least one m.:

      Progressive decline in R. func. (s. cr.).  or/+

      Persistent active ur. sediment (dysmorphic hematuria+/-RBCs casts) or/+

      Persistent or new appearance of extra active vasculitis}.

True Cph. resist. must be DD. fr. Sns of permanent dge occ. by previous R. active dis. (e.g, S. cr. with or without Prot in abs. of dysmorphic hematuria), pres. of other dis. & medication toxicities (eg, infec.) tht may present é C.P similar to active dis.. Incidence of resistance: 10 % in trials, but higher in clinical practice (23% in one series). Risk f. for resistance incl.:Ö[female sex, black ethnicity & sev. kid. dis. at presentation]. Ptns é Cph. resist. hv poor prognosis: 79 % ESRD at  median of 2 m. after start of therapy. Rate of ESRD ws much lower in ptns attained remission é initial im/m. ttt .

True resistant+ active inflmm.: 1^st step ensure Cph. ws optimized & Pph hs bn tried.  Definitive persistent active dis. é mj. organ & if optimal Cph dosing is in-effective or not tolerated trial of either➳ MMF:500 mg/twice/d. wch’s incr., if no response, by 250 mg/twice/d. every 2 w., max.: 1500 mg /twice/d., or ➳ rituximab: 375 mg/m2/w./4 w.