Shout out to Paige for admitting the interesting young woman with no medical history who presented with blurry vision, found to be in hypertensive emergency and nephrotic syndrome. Her work up revealed diffuse proliferative lupus nephritis (class IV) without any other clinical features of lupus!
Proteinuria is primarily caused by three processes: 1) overflow (due to elevated paraprotein levels), 2) glomerular disease, 3) tubular disease (rarely reaches nephrotic range)
Renal involvement is noted in ~50% of patients with SLE and can present as nephrotic and/or nephritic syndromes.
The most common and severe form is diffuse proliferative lupus nephritis (class IV)
Keep in mind that SLE flare is associated with a normal/low WBC, normal/low CRP, and absence of fever. Infection, which can instigate a lupus nephritis flare, would cause an elevated WBC, elevated CRP, and fever.
Lab findings suggestive of SLE flare also include an elevated anti-dsDNA (correlates with disease activity), low complement levels (especially C3), worsening proteinuria, and elevated creatinine.
Treatment involves an induction phase with cytoxan or MMF plus solumedrol followed by a maintenance phase with the goal of reducing urine protein excretion to <0.33 g/day.
Urgency: BP>180/120 without end organ damage
Manage with orals, goal to lower (not necessarily correct) over 24-48 hours
Emergency: elevated BP + end organ damage (brain, eye, heart, kidney)
Manage with IV meds, reduce DBP by 10-15% over the first hour, then by 25% over the next 6-12 hours.
Lower rapidly in acute aortic dissection (goal SBP <110 ASAP)
Recent ischemic stroke: do not lower BP unless > 220/120 (> 185/110 if received reperfusion therapy)
Female to male prevalence is 9:1
Diagnose using Systemic Lupus International Collaborating Clinics (SLICC) criteria. Must have > 4 (at least 1 clinical and 1 laboratory) OR biopsy proven lupus nephritis with a positive ANA or dsDNA
dsDNA is 50% sensitive but 97% specific –> can monitor disease activity
Smith is 10-20% sensitive but >90% specific
Work up of presumed flare:
Important to distinguish flare from acute infection but keep in mind that infection can trigger flare
Low WBC and normal CRP (except when serositis is present)
Jonathan presented a case of a 39yo M with no significant medical history, presenting with 1 month of non-improving dry cough, dyspnea on exertion, subjective fevers, and leg weakness. His CK was significantly elevated on admission to 27k, and CXR revealed peri-hilar lung base opacities which could represent pneumonia. His exam was significant for debilitating proximal muscle weakness (distal strength was intact!) with hyporreflexia. Ultimately Anti-Jo1 antibodies returned positive, and CT Cx revealed predominantly lower lobe GGO without evidence of honeycombing or traction atelectasis. This constellation of findings (myopathy, lung pathology, anti-synthetase antibody positivity) is consistent with Anti-synthetase syndrome!
Up to 30% of patients with DM or PM will have this constellation of clinical findings, terms Anti-Synthetase syndrome.
More acute onset of the following:
Presentation: Often acute
Constitutional symptoms i.e. fever
ILD: Often severe and rapidly progressive, frequently predominates other symptoms
Cardiac arrhythmias or ventricular dysfunction
Poorly defined as a condition, but in general, diagnostic criteria based on expert consensus is positive antisynthetase antibodies plus at least 1 feature
Antibodies to aminoacyl-rRNA synthetases (antisynthetase antibodies), i.e. Anti-Jo1 (most common)
Anti PL-7 & PL12 (seen in pts with predominantly ILD sx, often very severe)
If antiRo or ANA present, suspect more of an myositis associated ILD
Most common findings are traction bronchiectasis, GGO
Diagnosis usually is made by combination of CT findings, serology, PFT, and clinical findings.
Often requires multiple immunosuppressives for symptomatic control.
First line: Corticosteroids, monotherapy associated with more frequent lung disease recurrence
Other agents often added i.e. azathioprine, mycophenolate, tacrolimus, rituximab, cyclophosphamide.
Our case today is a 49 year old woman with no medical history, presenting with 1 month of difficulty swallowing, voice changes, and more recently dysphagia with liquids and solids, and shortness of breath. Her symptoms are worse during the night time to the point that she couldn’t swallow her own spit/secretions. She presented with respiratory failure requiring intubation, and on CXR/CT she was found to have an anterior mediastinal mass concerning for a… thymoma!
Let’s first briefly review Myasthenia Gravis before moving onto Myasthenia Crisis, and lastly, Thymomas.
Bimodal: Early peak in 2-3rd decades (female predominance) and late peak 60-80s (male predominance).
F in post-partum period have inc risk.
Possible association with: neuromyelitis optical, autoimmune thyroid disorders, SLE, RA.
Ice-pack test: Improvement of ptosis after application of an ice pack = positive. Sensitivity around 80ish %, limited to patients with ptosis and not helpful for those with extraocular muscle weakness.
Source: NEJM, Grepmed
Edrophonium test is no longer used very often, in a nut shell, it is a Acetylcholinesterase inhibitor with rapid onset (within 30-45 seconds), produces improvement of affect muscles after injection.
80-90% sensitivity but high rates of false positive. Not very specific.
Serology (seropositive in 90% of MG patients).
Titers do not correlate with disease activity
85% positive in generalized MG
Highly specific, extremely low false positives (LE, certain motor neuro dz, polymyositis)
Seen in 38-50% with generalized MG who are AChR Ab negative.
Thymoma patients with MG: 98-100% will have positive AChR-Ab.
NPPV for thymoma in the absence of AChR-Ab is 99.7%
Seronegative: 6-12%, more likely to have purely ocular myasthenia.
EMG: Can help confirm diagnosis
Single fiber EMG
Abnormal in > 90% of those with generalized MG, less so in ocular MG
Most sensitive diagnostic test for MG, 90-95% sensitivity (les for ocular MG), 91% specific.
Repetitive nerve stimulation
Readily available but less sensitive vs SFEMG
Nerve is stimulated multiple times, and the compound muscle action potential is recorded, test is considered positive if progressive decline in CMAP readings with the first 4-5 stimuli.
Symptomatic: Pyridostigmine, max daily dose 7mg/kg
Too much pyridostigmine can cause cholinergic crisis, leading to—weakness. Chances of this dec by limit daily dose of pyridostigmine to less than 960mg daily
Chronic immunotherapy: Required for those with sx on pyridostigmine or recurrence of sx on pyridostigmine after initial improvement.
Steroids or immunosuppressives i.e. azathioprine, mycophenolate, cyclosporine.
Thymectomy: Recommended for age < 60, has been considered beneficial even without presence of a thymoma.
Definition: Weakness severe enough to impair muscles of respiratory requiring mechanical ventilation.
10-20% of pts with MG will experience at least one crisis, annual risk 2-3%
For 13-20% of pts with MC, the crisis is their first clinical manifestation of MG and initial diagnosis.
Most occur in the first few years after diagnosis of MG.
Progressive generalized or bulbar weakness leading to respiratory failure.
Variable presentation in terms of degree of weakness (general vs respiratory)
May be precipitated by: infection, surgery, pregnancy, childbirth, medication tapering, certain drugs (beta blockers, antibiotics), magnesium
Airway/Breathing: Monitor respiratory muscle strength frequently, should be admitted to MICU
Indications for intubation:
FVC < 15 – 20 mL/kg
NIF < -25 to -30 cmH2O (i.e. 0 to -24)
PCO2 > 50
Difficulty with secretions
Intubation if signs of impending respiratory failure.
Elective intubation, rather than emergent, is preferred.
Rapid IVIG or plasma exchange, FAST
Plasmapheresis directly removes acetylcholine receptor ab in the circulation
High dose glucocorticoids, azathioprine, cyclosporine, or mycophenolate
Wean as respiratory muscle strength improves after completing or IVIG or plasma exchange.
Aggressive pulmonary toilet.
Pyridostigmine generally avoided after intubation temporarily since it might increase secretions, leading to more complex pulmonary care.
Can be resumed after extubation.
Median age 40-60
Men ~ Women
No known risk factors but strong association with myasthenia gravis
Local thoracic symptoms
Up to ½ of pts with thymoma will have MG like sx.
MG is common with thymomas but rare in thymic carcinoma
Neuro: MG, polymyositis, Lambert Eaton, Isaac’s syndrome, stiff person syndrome
Heme: Pure red cell aplasia, hemolytic anemia, pernicious anemia, agranulocytosis
Today, we talked about the case of a middle-aged man with history of diabetes, HTN, and A fib who presented with acute onset of progressive painful palpable purpura on his extremities, found to be cutaneous small vessel vasculitis on skin biopsy!
Purpura implies problem at the level of vessel. It can be divided into
Non-palpable purpura: petechiae (<3mm) or ecchymoses (>3 mm) and are usually associated with disorders of coagulation and platelets.
Palpable purpura: suggests inflammation and possible vasculitis.
Cutaneous small vessel vasculitis: disease limited to skin without any systemic vasculitis or glomerulonephritis
LCV: histopathologic term defining vasculitis of small vessels
Hypersensitivity vasculitis: small vessel necrotizing vasculitis
Immune complex small vessel vasculitis: associated with immune complex and/or complement deposition. If limited to skin, this is identical to cutaneous small vessel vasculitis. If not limited to skin, then other etiologies like cryo, SLE, Sjogren, RA, anti-GBM, IgA, etc.
Approach to purpura
Hypersensitivity (in the normal complement category of vasculitis) can result from medications/drugs as well as certain conditions such as HIV.
Numerous meds can cause LCV including some common ones such penicillins, cephalosporins, sulfonamides (including most loop and thiazide-type diuretics), phenytoin, and allopurinol have been most often implicated
Cutaneous small vessel vasculitis:
Lesions can coalesce, ulcerate or be surrounded by hemorrhagic bullae
No visceral organ involvement in CSVV. However, it can occur later in the disease course.
Start with checking serum complement levels to guide your need for further laboratory work up!
Management and Prognosis:
Usually self limited and resolved within 2-4 weeks
Rest, elevate, compression stockings
If complicated (presence of hemorrhagic blisters, cutaneous necrosis, or ulceration can lead to secondary infections, chronic wounds, and scarring)
Systemic glucocorticoids (oral steroids): pred 0.5 mg/kg of ideal body weight until new lesion formation ceases, then taper over 3-6 weeks
If relapse with prednisone: then colchicine or dapsone
If refractory: then azathioprine, methotrexate, and MMF
Example of palpable purpura with hemorrhagic blisters:
Today, we talked about the very interesting case of a middle-aged man who presented with acute migrating oligoarthritis, found to be febrile with an inflammatory synovial fluid and elevated ASO titers consistent with acute rheumatic fever!
Nonsuppurative manifestations of GAS infection include acute rheumatic fever (ARF), acute GN, and Scarlet fever.
Use the modified Jones Criteria to help you diagnose ARF and treat early if high suspicion for the disease (do not wait for titers to come back).
Late complications of ARF include rheumatic heart disease (10-20 years after infection) and Jaccoud arthropathy.
Treatment of ARF involves NSAIDs for arthritis, PCN G IM x 1 dose for acute presentation and then monthly for prophylaxis, and patient education about oral hygiene to prevent endocarditis and need for prophylaxis before invasive procedures.
Differential diagnosis for a migratory arthritis
Vasculitis (IgA, cryo, ANCA associated)
Bacteremia (staph, strep, mening/gonococcal)
Pulmonary infections (mycoplasma, histoplasma)
Nonsuppurative complications of GAS infection
Nonsuppurative sequela that occurs 2-4 weeks after GAS pharyngitis
More common in children 5-15 years of age
More common in resource limited settings
Poorly understood, ?molecular mimicry
Two primary manifestations of disease
(Table above from UpToDate)
Rheumatic heart disease (10-20 years after infection), primary involves the mitral valve >aortic valve.
Leading cause of cardiovascular death in the first 5 decades of life in resource limited settings
Revised Jones criteria (joint and cardiac manifestations can only be counted once).
Carditis and valvulitis (clinical or subclinical) – 50-70%
Usually pancarditis. Valvulitis especially of mitral and aortic valves, shown as regurg on echo.
Carey Coombs murmur: short mid-diastolic murmur heard loudest at the apex
Arthritis (migratory, involving large joints) – 35-66%, earliest symptom
Several joints affected in quick succession, each inflamed for a day or two to one week. Most common are knees, ankles, elbows, and wrists.
CNS involvement (Sydenham chorea) – 10-30%
Subcutaneous nodules – 0-10%
Erythema marginatum – <6%
Elevated acute phase reactants (ESR, CRP)
Prolonged PR interval on EKG
Diagnosis requires evidence of prior GAS infection plus:
2 major OR
1 major + 2 minor criteria OR
3 minor criteria (only if patient has history of prior episode of ARF)
In a high prevalence setting, slightly modified criteria are used.
Prior GAS infection through either
Positive rapid strep antigen test
Elevated or rising ASO titers
Symptomatic relief of acute disease manifestations
Carditis: if severe, heart failure treatments
Eradication of GAS
IM PCN G benzathine x 1
Contacts (throat culture test and treat if positive)
Ppx against future GAS infection to prevent progression of cardiac disease
PCN G IM once a month
For 5 years or until 21 years of age (whichever is longer)
If ARF with carditis and residual heart disease
10 years or until 40 years, sometimes even lifelong
Thanks to Tim for presenting the interesting case of a middle-aged man with h/o inadequately treated syphilis who presented with neck stiffness worse in the mornings, back pain, and blurry vision, admitted for presumed neurosyphilis. Exam revealed inflammation of T2/T3 joints, L SI joint tenderness, and an inflamed R foot with dactylitis of the 3rd and 4th digits. Further history revealed a recent gonorrhea/chlamydia for which he was treated and HLA B27 positivity consistent with reactive arthritis! He was started on NSAIDs with significant improvement of symptoms.
Neurosyphilis is most commonly seen in HIV positive patients and can present at any time after infection.
Early neurosyphilis occurs within the first year after infection and involves the CNS, meninges, and vasculature
Neurosyphilis presents with posterior uveitis or pan-uveitis whereas reactive arthritis presents with anterior uveitis
Late neurosyphilis occurs >10 years after infection and involves the brain and spinal cord parenchyma
The four main spondyloarthropathies are ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and IBD-related arthritis.
The genital pathogen most commonly associated with reactive arthritis is chlamydia trachomatis.
Ernest presented a case of a young woman, with no medical history, presenting with acute onset severe mucositis (eyes, mouth, urogenital) after a few days of viral prodrome and one day after taking azithromycin prescribed by her PCP. Her skin findings were almost non-existent and the bulk of her symptoms were isolated to the mucosa. Her presentation is consistent with a diagnosis of MIRM!
MIRM (Mycoplasma Induced Rash and Mucositis)
25% of patients with mycoplasma pneumoniae experience extra-pulm manifestations
Coined different terms, incomplete SJS, Fuchs Syndrome, MIRM
Mean age: Young (median 11-12 yo), male predominance.
Universally will have some sort of prodrome: cough, malaise, fever preceding eruption of lesions by ~ 1 week.
Manifestations: variable, mucositis alone, prominent mucositis with sparse skin involvement. Skin involvement tends to be very rare and on the milder side, presenting as vesiculobullous, targetoid, papules, macules. Rarely morbilliform.