SLE resident survival guide

SLE Resident Survival Guide
Overview
Causes
FIRE
Diagnosis
Treatment
Do's
Don'ts

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Iqra Qamar M.D.[2]; Aditya Ganti M.B.B.S. [3]

Overview

Causes

• Genetic predisposition:
  • HLA class polymorphism
  • Complement genes
  • Female sexual gene due to high levels of estrogen and prolactin
• Auto-immune disease

• Infections
  • Parvovirus B19
  • Epstein-Barr virus (EBV)
  • Trypanosomiasis
  • Mycobacterial infections 

• Exposure to ultraviolet (UV) light
  • Can exacerbate or induce systemic manifestations of SLE 
• Drug-induced lupus

FIRE

Diagnosis

Diagnostic criteria:

In 2012, Systemic Lupus International Collaboration Criteria (SLICC) developed a new criteria for SLE diagnosis. SLICC criteria for the classification of systemic lupus erythematosus was developed based on the old ACR criteria for the classification of systemic lupus erythematosus to address a more sensitive diagnostic criteria and also to cover weaknesses of the previous ACR criteria.

Based on SLICC criteria, diagnosis of SLE is defined as:

• Meeting at least 4 of 17 criteria, including at least 1 of the 11 clinical criteria and one of the six immunologic criteria 

OR

• Biopsy-proven nephritis compatible with SLE in the presence of antinuclear antibodies (ANA) or anti-double-stranded DNA (dsDNA) antibodies

A criterion is considered positive if one or more of the observations listed in the definition for the criterion are present in the patient. A criterion should only be counted once, regardless of the number of observations in the definition that the patient presents with.

Category	Criterion	Definition
Clinical	Acute cutaneous lupus	Lupus malar rash Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds Bullous lupus Toxic epidermal necrolysis variant of SLE Maculopapular lupus rash Photosensitive lupus rash (in the absence of dermatomyositis); Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation   Subacute cutaneous lupus Nonindurated psoriaform and/or annular polycyclic lesions that resolve without scarring, although occasionally with postinflammatory dyspigmentation or telangiectasias
	Chronic cutaneous lupus	Classic discoid rash Localized (above the neck) Generalized (above and below the neck) Hypertrophic (verrucous) lupus Lupus panniculitis (profundus) Mucosal lupus Lupus erythematosus tumidus Chilblains lupus OR Discoid lupus/lichen planus overlap
	Nonscarring alopecia	Diffuse thinning or hair fragility with visible broken hairs (in the absence of other causes, such as alopecia areata, drugs, iron deficiency, and androgenic alopecia)
	Oral or nasal ulcers	Palate, buccal, tongue, or nasal ulcers (in the absence of other causes, such as vasculitis, Behçet's disease, infection, inflammatory bowel disease, reactive arthritis, and acidic foods)
	Joint disease	Synovitis involving two or more joints, characterized by swelling or effusion Tenderness in two or more joints and at least 30 minutes of morning stiffness
	Serositis	Typical pleurisy for more than one day, pleural effusions, or pleural rub Typical pericardial pain (pain with recumbency improved by sitting forward) for more than one day, pericardial effusion, pericardial rub, or pericarditis by electrocardiography in the absence of other causes, such as infection, uremia, and Dressler's syndrome
	Renal	Urine protein-to-creatinine ratio (or 24-hour urine protein) representing 500 mg protein/24 hours Red blood cell casts
	Neurologic	Seizures Psychosis Mononeuritis multiplex (in the absence of other known causes, such as primary vasculitis) Myelitis Peripheral or cranial neuropathy (in the absence of other known causes, such as primary vasculitis, infection, and diabetes mellitus)  Acute confusional state (in the absence of other causes, including toxic/metabolic, uremia, drugs)
Hematologic	Hemolytic anemia	Hemoglobin less than 12 g/dL in females and 13 g/dL in males
	Leukopenia or lymphopenia	Leukopenia (<4000/mm3 at least once) (in the absence of other known causes, such as Felty's syndrome, drugs, and portal hypertension) Lymphopenia (<1000/mm3 at least once) (in the absence of other known causes, such as glucocorticoids, drugs, and infection)
	Thrombocytopenia	Thrombocytopenia (<100,000/mm3) at least once in the absence of other known causes, such as drugs, portal hypertension, and thrombotic thrombocytopenic purpura
Immunologic	ANA	ANA level above laboratory reference range
	Anti-dsDNA	Anti-dsDNA antibody level above laboratory reference range (or >twofold the reference range if tested by ELISA)
	Anit-SM	Presence of antibody to Sm nuclear antigen
	Antiphospholipid	Antiphospholipid antibody positivity as determined by any of the following: Positive test result for lupus anticoagulant False-positive test result for rapid plasma reagin Medium- or high-titer anticardiolipin antibody level (IgA, IgG, or IgM) Positive test result for anti-beta 2-glycoprotein I (IgA, IgG, or IgM)
	Low complement	Low C3 Low C4 Low CH50
	Direct Coombs' test	Direct Coombs' test in the absence of hemolytic anemia

Complete diagnostic approach:

SLE Presentation Fatigue Fever Myalgia Joint tenderness Muscle weakness Weight changes Less common Presentation Dysphagia Peptic ulcer disease Intestinal pseudo-obstruction Protein-losing enteropathy Acute pancreatitis Pneumonitis Pleuritis Pulmonary hemorrhage Interstitial lung disease Pulmonary emboli Pulmonary hypertension Pericarditis Myocarditis Seizures Stroke Psychosis Nephrotic syndrome
Focused History Onset, duration and progression of symptoms History of weight changes (gain or loss) Anorexia Arthritis, arthralgias, or muscle pain Morning stiffness Skin rashes and their association to flare ups, especially after exposure to sunlight Medications and their association to flare ups Infections especially mononucleosis Sores in the mouth, nose, or other mucous membranes Symptoms of other organ failure Renal failure: Recent peripheral edema and weight gain Cardiac involvement: Tachycardia, dyspnea, chest pains History of having a pet Hair loss Job history Co-morbid conditions include: Other rheumatologic and autoimmune diseases Hypertension Diabetes, immunodeficiency Seizures, or other nervous system symptoms Family history of rheumatologic diseases
Physical Examination Appearance of the Patient Patient appears well in the earlier stages of the disease Patient appears ill in the late stages of the disease due to multi-organ involvement Vital Signs Fever higher than 38 after the exclusion of infection Tachycardia/bradycardia depends on the accompanying complication Tachypnea/bradypnea depends on the accompanying complication Skin Cyanosis Secondary to respiratory complications Jaundice Secondary to hepatitis Pallor Secondary to anemia Generalised erythema Bruises Secondary to thrombocytopenia Urticaria Bullous lesions Sclerodactyly Skin ulceration Malar rash: the classic lupus ‘butterfly’ rash Erythematous, elevated lesion, pruritic or painful, in a malar distribution, commonly precipitated by exposure to sunlight Annular or psoriasiform skin lesions Small, erythematous, slightly scaly papules that evolve into either a psoriasiform (papulosquamous) or annular form and tend to involve shoulders, forearms, neck, and upper torso Scarring chronic alopecia Mostly present on face, neck, and scalp Telangiectasias Dyspigmentation (hyperpigmentation or hypopigmentation) of skin in scar places Follicular plugging Discrete, erythematous, slightly infiltrated plaques covered by a well-formed adherent scale that extends into dilated hair follicles Nodules Can be firm (Lupus profundus) and painful Photodistributed lesions with chronic pink indurated plaques or broad lesions that are slow to heal (more seen in lupus tumidus) Thin hair that easily fractures (lupus hair) Irregularly shaped raised white plaques, areas of erythema, silvery white scarred lesions, and ulcers with surrounding erythema on the soft or hard palate or buccal mucosa Periungual erythema Dilated tortuous loops of capillaries and a prominent subcapillary venous plexus along Involves the base of the nail and edges of the upper eyelid For more pictures of the rash presentation in lupus, click here. HEENT Ophthalmology Nystagmus Visual retinal changes from systemic lupus erythematosus cytoid bodies, retinal haemorrhages, serous exudate or haemorrhage in the choroid, optic neuritis (not due to hypertension, drugs or infection) Cataract Optic nerve atrophy Icteric sclera Cotton wool spots in the retina in ophthalmoscopic exam Nasal ulcers Mostly painless Mostly in lower nasal septum and bilateral and parallel Nasal perforation secondary to vasculitis may happen rarely Oral ulcers Mostly painless White plaques with areas of erythema, or punched-out erosions or ulcers with surrounding erythema on the soft or hard palate or buccal mucosa Neck Jugular venous distension Secondary to hypertension and cardiac complications Lymphadenopathy Lymph nodes are soft, non-tender, discrete Usually detected in the cervical, axillary, and inguinal Lungs Fine and coarse crackles upon auscultation of the lung May be due to pneumonitis In case of pleural effusion: Asymmetric tactile fremitus Asymmetric chest expansion Heart Chest tenderness or discomfort upon palpation May be due to costochondritis Diastolic murmur, or systolic murmur >3/6 due to valvular disease Loud second heart sound (due to pulmonary hypertension) Loud S1-S2 due to cardiomegaly Decrease heart sounds if associated with pericardial effusion Abdomen Abdominal distention Ascites Due to nephrotic syndrome Abdominal pain Due to mesentric vasculitis Hepatomegaly Splenomegaly Costo-vertebral angle tenderness Extremities Clubbing Cyanosis Muscle atrophy or weakness Livedo reticularis Reddish-cyanotic, reticular pattern on the skin of the arms, legs, and torso, particularly with cold exposure Arthritis Symmetrical Polyarticular Mostly involve knees, carpal joints, and joints of the fingers, especially the proximal interphalangeal (PIP) joint Decrease range of motion in affected joints Joints erythema Due to synovitis Joint effusion Muscle atrophy Fasciculations in the upper/lower extremity Claudication Loss of digit or limb Neuromuscular Patient is usually oriented to persons, place, and time based on the disease course Cognitive impairment Hallucinations Visual Auditory Memory deficit Loose associations Impoverished thought content Illogical thinking Bizarre disorganised or catatonic behaviour
Laboratory Workup CBC with DC SMA-7 Creatine kinase Urinalysis with microscopic examination Erythrocyte sedimentation rate C-reactive protein Coombs test Antinuclear antibodies Rheumatoid factor Cryoglobulins Antiphospholipid antibodies Complement levels Urine protein-to-creatinine ratio Anti-dsDNA antibody Anti-SM antibodies Anti-Ro/SSA antibodies Anti-La/SSB antibodies Anti-U1 RNP antibodies Antiribosomal P protein antibodies
Imaging Study Plain radiographs of swollen joints Erosions Ultrasonography of painful joints Detect synovitis and tenosynovitis in the hands and wrists in patients with SLE Renal ultrasonography To assess kidney size To rule out urinary tract obstruction Chest radiography For suspected pleural effusion, interstitial lung disease, cardiomegaly Echocardiography For suspected pericardial involvement, to assess for a source of emboli, or noninvasive estimation of pulmonary artery pressure; and for evaluation of suspected valvular lesions, such as verrucae Computed tomography (CT) For abdominal pain, suspected pancreatitis, interstitial lung disease Magnetic resonance imaging (MRI) For focal neurologic deficits or cognitive dysfunction
Other Investigation Bronchoscopy Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsies: To substantiate the diagnosis of alveolar hemorrhage Barium swallow or esophagography Esophageal stricture Peptic strictures that appear as smooth, tapered narrowing in the distal esophagus Esophageal dilatation Biopsy Renal biopsies: Determining the degree of renal involvement Delineating treatment decisions and prognosis in certain clinical scenarios Assess activity and damage (i.e., chronicity) Helping with classification Endomyocardial biopsy: May be helpful in guiding treatment towards the use of corticosteroids Paracentesis Paracentesis in the presence of the following conditions either for symptomatic relief (therapeutic) or fluid evaluation (diagnostic): Ascites Massive pleural effusion Massive pericardial effusion and tamponade Arthrocentesis In the presence of joint effusion to differentiate between different causes of arthritis

Treatment

Treatment goals Treatment goals in systemic lupus erythematosus (SLE) include: Ensure long-term survival Achieve the lowest possible disease activity Prevent organ damage Minimize drug toxicity Improve quality of life General treatment Hydroxychloroquine: 200 to 400 mg daily as a single daily dose or in 2 divided doses. Generally, all patients with any type of SLE manifestation should be treated with hydroxychloroquine regardless of the severity of the disease. The treatment choice for systemic lupus erythematosus (SLE) is varied based on the severity of the disease and symptoms: Mild cases are defined as disease pattern with one or two organ involvement. Moderate cases are defined as more than 2 organ involvement during disease flares with low grade of involvement and complications or one or two organ involvement with more extensive involvements. Severe cases are defined as presentation of the disease with life threatening complications and multiple (more than 2) organ involvements. Severe disease Preferred regimen (1): Hydroxychloroquine PO 200 to 400 mg daily as a single daily dose or in 2 divided doses AND methylprednisolone as intravenous "pulse"; 0.5 to 1 g/day for three days in acutely ill patients, or 1 to 2 mg/kg/day in more stable patients Alternative regimen(1): Hydroxychloroquine PO 200 to 400 mg daily as a single daily dose or in 2 divided doses AND prednisone oral; 40-60 mg/day Alternative regimen (2): Mycophenolate For induction: 1 g twice daily for 6 months in combination with a glucocorticoid For maintenance: 0.5-3 g daily or 1 g twice daily Initial period of intensive immunosuppressive therapy (induction therapy) to control the disease and halt tissue injury Alternative regimen (3): Cyclophosphamide IV 500 mg once every 2 weeks for 6 doses or 500 to 1,000 mg/m2 once every month for 6 doses or 500 to 1,000 mg/m2 every month for 6 months, then every 3 months for a total of at least 2.5 years Alternative regimen (4): Rituximab IV: 375 mg/m2 once weekly for 4 doses or 1,000 mg (flat dose) on days 0 and 15 or 500 to 1,000 mg on days 1 and 15 Less Severe (mild and moderate) disease Preferred regimen (1): Hydroxychloroquine PO 200 to 400 mg daily as a single daily dose or in 2 divided doses Preferred regimen (2): Prednisone PO low doses of 10 mg/d or less for a short term therapy For milder SLE For treatment of cutaneous and musculoskeletal symptoms not responding to other therapies It should be tapered once hydroxychloroquine has taken effect Alternative regimen (1): Azathioprine PO initial 2 mg/kg/day; may reduce to 1.5 mg/kg/day after 1 month Can be used to control symptoms Alternative regimen (2): Methotrexate PO initial therapy with 7.5 mg once weekly; may increase by 2.5 mg increments weekly Can be used to control symptoms Other organ specific treatments Fever management Preferred regimen: Celecoxib PO 100 to 200 mg twice daily For fever management even in SLE patients with “sulfa” allergy Alternative regimen: Acetaminophen 1000 mg every 6 hours; maximum daily dose: 3000 mg daily  Raynaud's phenomenon treatment Preferred regimen (1): Calcium channel blocker (nifedipine) 10 to 30 mg 3 times daily Preferred regimen (2): Antiplatelet therapy with low-dose aspirin (75 or 81 mg/day) in all patients with secondary Raynaud phenomenon Alternative regimen (1): Phosphodiesterase (PDE) inhibitor (sildenafil) 20 mg once or twice daily Inadequate response to a CCB Alternative regimen (2): Addition of topical nitroglycerin (NTG) Inadequate response to a CCB A PDE inhibitor is not available, effective, or well-tolerated Alternative regimen (3): Intravenous (IV) infusions of a prostaglandin (PG) especially prostacyclin (PGI2) analogue for extremely severe patients with raynaud's phenomenon Chronic pain management Moderate pain should be treated with mild prescription opiates such as: Preferred regimen: Dextropropoxyphene 600 mg maximum daily dosage divided into 2 or 3 doses Alternative regimen: Co-codamol (Acetaminophene+opioid): Acetaminophen (300 to 1,000 mg/dose)/codeine (15 to 60 mg/dose) every 4 hours as needed; adjust dose according to severity of pain and response of patient (maximum: acetaminophen 4,000 mg/codeine 360 mg per 24 hours) Moderate to severe chronic pain should be treated with stronger opioids such as: Preferred regimen (1): Hydrocodone: Single doses >40 mg or >60 mg with a total daily dose ≥80 mg Preferred regimen (2): Oxycodone: 5 to 15 mg every 4 to 6 hours as needed Alternative regimen (1): MS Contin: Opioid naive patients can have 5 to 10 mg every 4 hours; usual dosage range between 5 to 15 mg every 4 hours Higher initial doses in patients with prior opioid exposure Alternative regimen (2): Methadone: Maximum initial dose 30 mg Alternative regimen (3): Fentanyl Duragesic Transdermal patch: A convenient treatment option for lupus chronic pain. It has a long lasting effect as well Cutaneous lupus erythematosus Preferred regimen (1): Super high potency or high potency topical steroid twice daily for patients with DLE or SCLE Hydrocortisone 1% or 2.5% for facial involvement Triamcinolone acetonide 0.1% cream or fluocinonide 0.05% cream: trunk, extremity, or scalp disease Clobetasol propionate for acute flares of DLE Discontinue treatment in the absence of disease activity Alternative regimen (1): Topical calcineurin inhibitor such as tacrolimus 0.1% ointment or pimecrolimus 1% cream Preferred regimen (2): Intralesional corticosteroid injections for DLE or SCLE if an acute flare of DLE or SCLE doesn't respond to topical steroid therapy for two to four week Alternative regimen (2): Systemic medications; hydroxychloroquine 200 to 400 mg/day for at least six weeks After improvement it should be decreased to 200 mg/day for maintenance therapy Administered in the case of failure of local therapy or extensive disease manifestation Alternative regimen (3): Quinacrine 100 mg/day In case of antimalarial drugs failure Lupus nephritis treatment Aggressive antihypertensive therapy with blood pressure goal of 130/85 In patients with proteinuria, antiproteinuric therapy with blockade of the renin-angiotensin system include ACEIs and ARBs: ACE inhibitors; captopril PO 25 mg 3 times daily Antiproteinuric effect  ARBs; losartan PO initial: 50 mg once daily; can be increased to 100 mg once daily based on blood pressure response Slowing progression of GFR decline; Lipid lowering with statin therapy with the goal of LDL< 130 Diffuse or focal proliferative LN: Preferred regimen: Immunosuppressive therapy with glucocorticoids plus either intravenous or oral mycophenolate mofetil: 0.5 g of mycophenolate mofetil twice daily for the first week, then 1 g twice daily for the second week, and thereafter increase the dose to 1.5 g twice daily Alternative regimen: Immunosuppressive therapy with glucocorticoids plus IV cyclophosphamide 500 mg every two weeks for a total of six doses Severe active disease:  Preferred regimen: Glucocorticoid therapy is initiated with intravenous pulse methylprednisolone (250 mg to 1000 mg given over 30 minutes daily for three days) to induce a rapid immunosuppressive effect, followed by conventional doses   Alternative regimen: Conventional doses of oral glucocorticoids (eg, 0.5 to 1 mg/kg per day of prednisone) without a pulse. Oral prednisolone at a dose of 60 mg/day, tapered every two weeks by 10 mg/day until 40 mg/day is reached, then tapered by 5 mg/day until 10 mg/day is reached  Considerations Appropriate adjunct therapy: Vitamin D and calcium supplements for preventing osteoporosis in patients using corticosteroids Antihypertensive drugs and statins were also recommended in patients using corticosteroids Adverse effects: Cutaneous atrophy is a potential side effect of the long-term use of topical steroids

Do's

Don'ts

References