Rheumatology Flashcards
Synovial fluid:
- Non-inflammatory
- Inflammatory
- Septic
Non-inflammatory:
-WBC <2000, <=50% PMNs, clear
Inflammatory
-WBC 10,000-100,000, >50% PMNs, turbid
Septic
- WBC >50,000 (bacterial), >80-90% PMNs, Cloudy/Pus
- WBC 10-30k (fungal or mycobacterial),
- High Sp if > 100,000
Diagnosis of RA
> 6 weeks duration (cutoff for chronic)
Inflammation of multiple joints (small >large), symmetric
Elevated inflammatory markers
Seronegative RA
- Seronegative RA of the elderly (age >60, shoulder and hip predominant + small joints
- RS3PE
RS3PE features + Mx
remitting seroneg symmetrical synovitis w/ pitting edema
Male >70
Pitting edema over dorsum of the hands
Tx: Low dose steroids, NSAIDs, Plaquenil
Extra-articular Manifestations RA
CV: Increased CAD risk, myopericarditis
Resp: ILD (NSIP>UIP), pleural effusions, pulm nodules, bronchiolitis obliterans
Eyes: Scleritis
Haem: Anemia chronic disease, Felty (neutropenia, splenomegaly, RA), Non-hodgkin’s lymphoma
Neuro: C1-2 instability/ subluxation, carpal tunnel
Skin/Mucous membranes: Sicca, nodules, vasculitis, raynauds
Treatment acute RA flare
Steroids (PO/IM/IA)
NSAIDs
Chronic RA Treatment
1st line: DMARDs (low dz activity =Plaquenil, Mod/High activity = MTX; other options SZS, LEF)
2nd line: Combine DMARDs *triple therapy no longer recommended
3rd line: Biologics (TNFi with MTX, then Toci/ abatacept/ ritux/ -tinibs / apremilast). Increase freq >dose when flare. Do not combine biologics.
*use ritux if pt also has lymphoproliferative d/i where ritux indicated
Methotrexate toxicities
Mucositis, oral ulcers
Nausea, vomiting, GI upset
Hepatotoxicity - can still use MTX in NAFLD if LE and LFT N and no advanced fibrosis
Rash, Alopecia
Pancytopenia
Hypersensitivity pneumonitis
ILD (rare) - can still use MTX in parenchymal lung dz that is incidental, mild, stable
Pre-MTX investigations
CBC, liver enzymes, Cr
CXR (get baseline)
Hepatitis B and C
Management of MTX-related NV or stomatitis
Increase folate to 5mg
Start ranitidine/PPI - for NV/GI upset
Trial leukovorin post MTX dose
Tx MTX related transaminitis
If <2x ULN: Decrease dose, do not need to hold
If >2x ULN: Hold, trend LE, resume at lower dose 1-2 wks post normalization
Tx MTX related cytopenia
Mild: Decrease Dose
Moderate-Severe: Hold, resume at lower dose once recovered
Tx MTX related pneumonitis
Discontinue permanently
Side effects leflunomide
Teratogenicity Rash Hepatotoxicity Cytopenias Peripheral neuropathy GI: N/V/D, abdo pain, dyspepsia
Side effects plaquenil
Retinotoxicity Photosensitivity Rash Myotoxic (rare) Cardiotoxic (rare)
Pre-biologic work-up for rheumatology
TBST or IGRA (if prev BCG)
CXR (if + TBST or high risk for Tb), if + –> sputum AFB
Hepatitis B sAg, sAB, cAb, HCV (treat concurrently if +)
CBC, Cr, LFTs
Pregnancy and RA
Plaquenil, SSZ, biologics safe
D/C methotrexate 1-3 months pre-conception (F)
D/C leflunomide 2 yrs pre-conception (or test lvls +/-cholestyramine washout)
Males preconception: Avoid Cyclo and thalidomide, MTX ok
Taper pred to <20 mg/day (<20 ok in preg)
Avoid NSAIDs esp in T3
Breastfeeding: Biologic and SFZ ok (risk of kernicterus), avoid MTX and LFD
Can flare postpartum (remission intrapartum)
Joint distribution in AS
Symmetrical Axial and SI involvement
Asymetrical large joints (if present)
Joint distribution in PsA
Asymmetrical axial/SI involvement (if present)
Peripheral can be either:
1) Asymmetric large joint
2) Symmetric small joint
Joint distribution in Reactive arthritis
Asymmetric large joint (mono or oligo)
+/- Asymmetric SI involvement
Joint distribution in IBD-associated arthritis
Type 1= Asymmetric large joint, assoc’d w/ bowel activity
Type 2= Symmetric small joint, indep of bowel
X-ray features in seronegative arthritis
SI: Sclerosis, Erosions, Ankylosis
Spine: syndesmophytes
MRI features in seronegative arthritis
Bone marrow edema
Syndesmophytes
Periosteal new bone formation (PsA)
Treatment seronegative arthritis
PT/Exercise/Smoking cessation for all
1st line: Trial of NSAIDs max dose daily x1 month
2nd line: Alternate NSAID x1 month
3rd line:
- If axial: anti-TNF –> IL-17 (secukinumab or ixekizumab) –> JAKi (Tofa)
- If peripheral: DMARDs (MTX, Sulfasalazine) - no role in axial
Risk factors for gout
M or Post-menopausal F Obesity, Metabolic syndrome CKD Hyperuricemia: TLS, hemolysis, polycythemia Meds: HCTZ, ASA, Pyrazinamide Diet: beer, meat, seafood
Treatment of Gout flare
NSAIDs
Colchicine (1.2mg load –> 0.6mg 1 hr later –> 0.6 BID till Sx resolve) - S/E: N/V?D, myopathy, renal dose
IA/PO steroid (if contraindications to above)
Anakinra (IL-1 blocker) - if frequent flares and C/I to above
Indications for urate lowering therapy
1) 2+ gout flares/year
2) Erosive gouty arthropathy
3) Tophi
4) 1 gout attack +
- Stg 3+ CKD
- Urolithiasis
- Uric acid >535
Urate lowering therapy
Overlap w/ NSAID/colch x 3-6mo:
1st line: Allopurinol* 100mg/d (50mg if CKD IV)
2nd line: Febuxostat (increased CV and all cause mortality, ie not if hx CVD or new CVD event)
Target uric acid <356
*In SE asian or african - test HLA-B 5801 1st bc risk SJS
CPPD features and RF
Rhomboid shaped, positively birefringent (blue parallel)
Chondrocal on XR
RF: Hypothyroidism, HyperPTH, HypoMg, HypoPO4 Hemochromatosis, Wilsons Amyloidosis Acromegaly
Acute destructive calcific tendinitis in older patient
Hydroxyapetite crystal arthropathy
SLE ACR Criteria
+ ANA 1:80 + Score >= 10 points from crit below
1) Constitutional Sx- Fever >38.3
2) Mucocutaneous: Non-scarring alopecia, discoid rash, malar rash, oral ulcers, photosensitive rash
3) Haem: low WBC <4, low plts <100, AIHA
4) Serosal: Pericarditis, pleuritis, effusions
5) CNS: Seizures, psychosis, delirium
6) Renal: Class II-V, proteinuria >0.5g/d
7) MSK: synovitis, arthalgias with morning stiffness
8) Serology +: Anti-dsDNA, Anti-Sm
9) Complements low
10) Positive APLA
*req 1 clinical criteria, and occurrence at least once is sufficient. Count highest score in each domain.
Lupus serology
ANA - sensitive, not spec
Anti-dsDNA - spec, not sensitive. Specific for SLE nephritis. Can be used to monitor dz activity.
Anti-Sm - specific, not sens
Other: histone, RNP, Ro, La
DDX ANA Positivity
AI Dz: RA, MCTD, Scleroderma, Myositis GI: Autoimmune hepatits, IBD, PBC Endo: AI thyroid disease Resp: IPF ID: HepC, TB, Parvovirus
Treatment SLE Nephritis
Class I/II: Supportive +/- immunosuppress if proteinuria >3g/d
Class III/IV (proliferative)
- Induction: Pulse steroids + Cyclo or MMF (if African or Hispanic) + ACEi if proteinuria
- Maintenance: MMF or Azathioprine, low dose pred. Ritux if refractory + ACEi if proteinuria
- In pregnancy: Stop ACEi, continue HCQ (+/- Aza for severe flare) and start ASA 12-36wks GA
Class V (membranous): BP Control, ACEi, consider immunosuppression if progressive renal function decline (re-bx)
SLE Manifestations and Tx: Mild, Mod, Severe
Mild: fever, mild arthritis, rash, mild cytopenias, plt 50-100
- HCQ +/- PO/IM steroid
- If refractory: +/- MTX or Aza
Moderate: RA-like arthritis, cutaneous vasculitis, serositis, moderate cytopenias Plt 20-50
- HCQ +/- PO/IM steroid +/- MTX or Aza
- If refractory: MMF or cyclosporin or Belimumab
Severe: CNS, class 3/4 nephritis, myelitis, pneumonitis, mesenteric vasculitis, severe cytopenias Plt <20, TTP, AIHA
- HCQ +/- PO/IM steroid +/- MMF or Cyclo
- If refractory: cyclo or ritux
Treatment Thrombotic-APS
Lifelong anticoagulation with warfarin
Transition to therapeutic LMWH in pregnancy and add ASA
Treatment OB-APS
Only requires prophylactic LMWH in pregnancy and post-partum + ASA
Management of SLE in pregnancy
- Meds
- Ro/La
- Positive aPL
HCQ in all, ASA 81 prior to 16wks GA for preeclampsia ppx
Azathioprine + steroid reasonable in severe disease
If Ro/La+: serial fetal echo from wk 16-26wks;
q1w if previous neonatal lupus.
-Dex if 1st/2nd deg heart block, not for 3rd
Positive aPL:
- No APS = ASA
- OB APS = ASA + ppx heparin until 6-12 wks pp
- Thrombotic APS = ASA + therapeutic heparin during preg and PP
Manifestations of Sjogren’s
Xerostomia (unstim saliv flow dx) Keratoconjunctivitis (Schirmer's test <5mm in 5 min) Arthritis Parotiditis (salivary gland bx shows focal lymphocytic sialadenitis) Peripheral neuropathy Type 1 RTA Secondary vasculitis B cell lymphoma (40x risk)
Diffuse Scleroderma - Manifestations
Sclerodactyly proximal to elbows/knees Face tightening Raynauds ILD > PH (TTE and PFTs for all pt) Scleroderma renal crisis
Limited Scleroderma- Manifestations
CREST Calcinosis Raynauds Esophageal dysmotility, GAVE (GIB) Sclerodactyly (distal to elbows/knees) Telangiectasias
Associated with PH >ILD (TTE and PFTs for all pt)
Scleroderma - Serology
Anti-centromere = limited (CREST; C for centromere)
Anti-Scl70 (aka anti-topoisomerase) - diffuse
Raynayds - red flags for secondary cause
Older age of onset (>40) Male Asymmetric, progressive Ulceration/pitting/ischemia Abnormal nailfold capillaries Positive serology
Secondary causes: SSc, MCTD, SLE, HypoT4, Carcinoid, pheo, HBV, HCV, Parvo, Heme Ca
Scleroderma renal crisis - features
Renal failure
+/-Hypertension
+/- proteinuria
MAHA, thrombocytopenia
Compared to TTP: less fever, purpuric rash
Treatment of Raynauds
1st line - CCB
2nd line- topical nitrates, PDE5 inhibitor
~to mx for chilblains (smoking cessation, cold avoidance, +/- topical steroid or CCB)
Inflammatory Myopathies (ie. myositis)
Dermatomyositis
Polymyositis
Necrotizing Auto-immune Myositis (secondary to statin)
Inclusion body myositis
Drug-induced myopathies
Statin Colchicine HAART EtOH Anti-psychotics, SSRIs, Li
Metabolic myopathies
Hypothyroidism
HypoPO4
HypoK
Infectious causes of myopathy
Influenza HIV Hep B CMV Bacterial pyomyositis
Skin manifestations of dermatomyositis
Gottren's papules Heliotrope rash Shawl Sign Mechanics hands Periungal erythema Calcinosis Cutis
End organ complications of dermatomyositis
CV: Myocarditis, CHF, arrhythmia
Resp: Diaphragmatic weakness, resp failure, Aspiration risk, ILD (NSIP, UIP), PH
Malignancy (DM>PM around dx)
Anti-Jo1
Anti-synthetase syndrome: Rapidly progressing ILD Mechanics hands, Raynaud's, skin ulceration Arthritis B-symptoms
Anti-Mi2
Classical dermatomyositis
Good response to tx/prognosis
Anti-NXP2 and TIF gamma
Strong association with underlying malignancy
Treatment of dermatomyositis (and IBM)
Steroids 1mg/kg then taper
DMARDs: MTX or Azathioprine
-Cyclo/MMF if ILD
-Plaquenil for skin only
2nd line: Ritux or IVIG for refractory disease
Clinical manifestations of Inclusion Body Myositis (IBM)
Distal + Proximal muscle weakness (distal>proximal)
Lower CK than DM
Progressive dysphagia and bulbar symptoms
Older, M>F, insidious
Treatment of statin associated muscle diseases
Myalgias (normal CK) - improves with d/c, can trial lower dose or alternate agent
Myopathy (weakness but normal CK) - D/C
NAM - D/C, requires imunosupression - confirm with HMG-CoA reductase antibody
Rhabdo - D/C, fluids and supportive care
Clues to Takayasu’s Arteritis
Female <40
Asian
Pulseless arm, BP differential
Subclavian steal
Features of PAN
HepB+ (in some)
B Sx: Fever, weight loss >4kg
Neuro: Mononeuritis multiplex/polyneuropathy
GI: Mesenteric arteritis - post-prandial abdo pain
GU: Orchitis - testicular pain/ tenderness, AKI
Derm: Livedo reticularis
cANCA/anti-PR3 positivity
GPA (few FPs)
MPA
pANCA/anti-MPO Positivity
incl false + causes
eGPA and Microscopic Polyangiitis False +: - IBD - Other CTDs - PTU use - Malignancy - HBV/HCV/HIV
Small vessel vasculitidies
ANCA-associated: GPA, eGPA, MPA
Anti-GBM (renal isolated or Goodpasture’s)
IgA (renal isolated or HSP)
Cryoglobulinemia - T1 = MM, T2/3 = HepC/mixed
Secondary SVV: Drugs (Levamasole), Infectious (Hep B, C), CTD Associated (SLE, Sjogren’s, RA), Malignancy (paraneoplastic, MM)
Variable sized vessel vasculitities
Buergers (thromboangiitis obliterans) - male smokers w/ hand/foot claudication
Behcets
Cogan
Treatment of GCA
Visual sx or critical cranial ischemia = IV pulse steroids 1gx3d then pred 1mg/kg + toci (for steroid free remission)
No visual sx: pred 1mg/kg daily + toci
No ASA unless critical or flow limiting involvement of carotid or vertebral arteries
Steroids x1mo then taper
Diagnosis PMR
- Bilateral shoulder and hip girdle pain
- 45 minutes or more am stiffness
- Elevated ESR/CRP, normal CK
- Negative RF/CCP
- US criteria: shoulder/hip bursitis/tenosynovitis
- Age >50
Treatment PMR
Prednisone 12.5-20 mg/day x2-4 wks then taper to 10mg/d within 1-2mo if response
If difficulty tapering, add MTX
Treatment of HepB Related PAN
Steroids + Anti-viral
+/- Plex if severe
Treatment of PAN (not-hepB associated)
Mild: Steroids +/- AZA or MMF
Moderate-Severe: Steroid + Cyclo –> Aza or MMF
Treatment of HepC Associated Cryoglobulinemia
*also describe features of mild/mod, severe, life threatening dz
If non-severe (non-ulcerating skin lesions, non-debilitating neuropathy, GN without renal failure): Induce: Antiviral +/- Steroid
Maintenance: Antiviral alone
If severe (ulcerating skin lesions, debilitating neuropathy, GN with renal failure, nephrotic syndrome, GI involvement): Induce: Steroid + Ritux 1st (alt= Steroid + Cyclo) Maintain: Antiviral alone
If life threatening (RPGN, CNS, DAH, GI ischemia):
Induce: Plex + Steroid pulse + Ritux or cyclo
Maintain: Antiviral alone
GPA Manifestations
*Nasal crusting, sinusitis, granulomas
Hearing loss
*Pulmonary nodules/ DAH/ Cavitary lung lesions
Subglottic stenosis
*Pauci-immune RPGN - hematuria, proteinuria
*Mononeuritis multiplex
Skin: Palpable purpura, nodules, PG, mucosal ulcers
Pericarditis/Myocarditis (rare)
Microscopic polyangiitis Manifestations
*Pauci-immune RPGN
*DAH, Pulmonary infiltrates, Fibrosis
Palpable purpura, nodules, lived reticular, necrotic ulcers
Symmetric peripheral neuropathy
eGPA Manifestations
Asthma, eosinophilia, Nasal polyps
Myopericarditis, arrythmias
Pauci immune GN
Mononeuritis multiplex, peripheral neuropathy
Induction ANCA Associated SVV
Induction:
-Pulse steroids 500-1000 mg IV x 3-5d + Ritux q4wks OR 1g IV day 1 and day 15
2nd line: Cyclo if C/I or failed ritux
-Cyclo preferred for RPGN with Cr >354
*No role for PLEX in DAH unless critically ill, or in RPGN unless high risk ESRD and accept infxn risk (KDIGO says PLEX for Cr >500)
Non-pharmacologic Tx of OA
For all: Exercise, self-efficacy program, arthritis society
Hip/knee: Weight loss, tai chi, cane, physio
*do NOT do transcutaneous electrical nerve stimulation in hip/knee OA
Pharmacologic Tx of OA
NSAIDs if no C/I Topical NSAIDs (evidence in knee OA only) IA Steroid (knee, hip, hand) Can consider: Tylenol, Duloxetine, Tramadol (caution if other SSRIs, hx of seizure or hypoglycemia)
NO: opioid, glucosamine, DMARDs, biologics, PRP, stem cell injxn, intra-articular hyaluronic acid
Diagnosis of Adult Onset Stills Disease (AOSD)
Dx >= 5 criteria (2 must be major) Major: - Fever >=39 x 1+ week - Non pruritic salmon rash - Arthritis or arthralgia >2weeks - WBC >10 with neuts >80%
Minor:
- Sore throat
- Splenomegaly or hepatomegaly
- Lymphadenopathy
- High liver enzymes
- High ferritin
- Negative ANA and RF
RF positive ddx
CTD Hep C Cryo IE Malignancy Older age
JAKi (-tinibs) side effects
Increased risk of MORTALITY, MACE, thrombosis, cancer
Biologic side effects and considerations
Infection (new/reactivation) Drug induced lupus (TNFi) Local skin rxn Malignancy eg non-melanomatous skin Ca PRES (IL12/23)
Considerations:
- TNFi: Heart failure - do not start if NYHA III/IV; switch to another agent if patient develops HF on TNFi
- Active hepatitis - start hep tx first, consult GI
- Use cDMARDs if prior skin Ca or serious infxn w/i 12mo
- Consult Onc if prior solid organ malignancy
Vaccinations on DMARDs or biologics (except Ritux)
Vaccinate during quiescent disease
If ritux, vaccine 4wks b4 starting or 6mo after last dose and 4wks before next dose
No live vaccine except HZV and possibly MMR booster
No live vaccine in 1st 6mo of newborns for mothers on biologics (eg no rotavirus vaccine)
Household members get normal vaccine except oral polio if living with immunosuppressed pt
Recommended vaccines:
Yearly influenza (hold MTX 2 weeks before and after)
Pneumococcal - PCV13 and PPSV23 8wks later
HPV, Tetanus toxoid - same as general popln
Hep A and B - only if high risk exposure
HZV - Shingrix preferred; live only if NOT on biologic or >4 weeks prior to biologic
Extraarticular features of seronegative arthropathies
- Enthesitis, dactylitis
- Uveitis, conjunctivitis
- Skin: erythema nodosum, pyoderma gangrenosum (IBD), keratoderma blenorrhagicum, circinate balanitis (reactive), psoriatic skin and nail changes (PsA)
Septic Arthritis Tx for G+, GPB/GPC
G+ community: Ancef
G+ hospital: Vanco
GNB: CTX + antipseudomonal if risk (DM, IVDU, hospitalized)
GNC (eg neisseiria, gonorrhea): CTX + tx chlamydia
Nothing on stain: Vanco + CTX
Source control: washout
Gonococcal arthritis
Triad: tenosynovitis, vesiculopustular skin lesions, migatory polyarthralgias (WITHOUT purulent arthritis)
If arthritis WITHOUT skin lesions = longer course of abx
Common bugs causing reactive arthritis
Chlamydia trachomatis, yersinia, salmonella, shigella, campylobacter
Reactive arthritis triad
Can’t see (uveitis, conjunctivitis)
Can’t pee (urethritis)
Can’t climb a tree (asymmetric oligoarthritis, lower>upper, can develop SI-itis)
Reactive arthritis Tx
NSAIDs
IA steroids
Consider DMARDs in recurrent/ chronic dz (eg MTX, SFZ, TNFi)
No role for abx unless active infxn
Malar rash vs Rosacea
Malar rash - spares nasolabial fold and worse with sun
Rosacea: freq flushing (hours), telangectasias, papules, pustules, aggravated by sun/spice/EtOH, can cross nasolabial fold
Cyclophosphamide S/E
Infertility
Malignancy: bladder, skin, MPD
Hemorrhagic cystitis
Cytopenias
MMF S/E
Unsafe in preg –> miscarriage, cleft palate
cytopenias
GI S/E
APS Tx
Heparin f/b warfarin (DOAC not recommended)
If Libman Sacks –> steroids + anticoag
Drug induced lupus Meds
Hydralazine, Procainamide, TNFi, Isoniazid
DM/PM Investigations
CK (can be normal in amyopathic DM - ie no weakness)
ANA, myositis ABs, AST, LDH, ESR/CRP
MRI
Biopsy (Gold standard)
EMG (irritability, low amplitude, repetitive discharge)
Trop, ECG, Echo (r/ cardiac involvement)
SLP r/o oropharyngeal, esophageal involvement
PFT w/ MIP, MEPs to r/o diaphragmatic involvement
Age appropriate Ca screening (consider CT C/A/P)
GCA LR
LR+: jaw claudication, beaded/tender temporal arteries
LR-: ESR
Maintenance ANCA Associated SVV
Maintenance:
- Severe dz: Steroid (reduced taper) + Ritux (if received for induction) or MTX/Aza > MMF or LFD
- Non-severe dz: Steroid (standard dose) + MTX
*In nonsevere: MTX preferred for induction & maintenance.
Relapse / Refractory ANCA Associated SVV
Relapse:
- If not on ritux maintenance –> Ritux
- If on Ritux maintenance –> Cyclo
Refractory :
- Switch agents to Ritux or Cyclo
- Add IVIG if refractory to remission induction
Medication management in COVID exposed and infected
Exposed:
- Continue NSAID and SFZ
- Hold Plaquenil, MTX, biologics pending 2wks symptom free observation
- Toci can be continued in some circumstances
Infected:
- Hold all meds except toci in some circumstances
- Hold NSAIDs if severe respiratory symptoms
Medication management in COVID vaccine setting
- Tylenol/NSAIDs - hold 24h prior to vaccination
- Plaquenil - no change
- DMARDs - hold 1-2 wks after vaccine
- Abatacept and Belimumab - 1-2 weeks btwn biologic and vaccine
- Other biologics: no consensus
Chilblains (aka pernio) Ddx
COVID 19 SLE, APS Behcet's Heme Ca (AML, CML, monoclonal gammopathy) Cryoglobulinemia
Fibromyalgia Dx Criteria + Tx
1) Widespread pain index and symptom severity scale
2) Symptoms >3mo
3) No other explanation
Bloodwork must be normal
Tx:
-Nonpharm: exercise, CBT, sleep hygiene, Tai chi
-Pharm: SNRI (dulox), TCA (amitriptyline), gabapentin
Relapsing polychondritis Tx
Mild (nasal / auricular chondritis, arthritis)
- NSAID
- Steroids or dapsone if fails NSAID
Mild/Mod organ threatening:
-Steroids + MTX
Life threatening or severe organ threatening:
-Steroids + cyclo
Still’s Disease Tx
Mild/Mod (nondisabling fever, rash, arthralgia, no MAS): NSAID
Mod/Severe (signif serositis, mod/severe polyarthritis, fevers despite NSAIDs, organ involved) or failed NSAIDs: Steroids or Anakinra
*if MAS present - etoposide + steroid
DDx scleritis (whites) and uveitis (middle; includes anterior iritis & posterior retinitis or choroiditis)
Scleritis: RA, polychondritis, SLE, reactive, Inxn (zoster, HSV, TB, syphilis), Sarcoid, IBD
Uveitis: Seroneg, HLAB27+, sarcoid, infxn (CMV, toxo, cat scratch, HSV)
