Parkinsonism

At physical exam rounds, we went over the examination for Parkinsonism. One approach:

Vital signs: Postural drop (autonomic dysfunction)

Face/head and neck:
-lack of facial expression "mask"
-lack of blinking
-drooling (autonomic dysfunction)
-brow for seborrhea (autonomic dysfunction)
-speech (soft, monotonous)
-cognitive dysfunction, depression

Extraocular movements for progressive supranuclear palsy (upward, then downward gaze palsy)- a "Parkinson's plus" syndrome

Special test: Glabellar tap- tell pt to look straight ahead, tap firmly on mid-forehead outside of the patient's visual field. Expect blinking with each tap x 5-10, then blinking should stop

Standing, gait:
-difficulty initiating movement (akinesis, bradykinesia)
-shuffling gait
-difficulty walking heel to toe
-freezing
-festination (small steps, seeming to "hurry")
-retropulsion (tendency to fall back)
-'en bloc' turning

Upper extremities
-resting tremor with arms relaxed (4-7 hz)
-tremor diminishes on finger to nose (vs. essential tremor, which increases with movement)
-wrist tone for cogwheeling; may look for activated rigidity (movement of opposite hand brings out cogwheeling)
-tests for bradykinesia: finger pinching (progressively smaller), rotation of hands, opposing thumb sequentially with each finger (may add while rotating other hand)
-micrographia

Lower extremities
-foot tapping: low amplitude, progressively smaller (bradykinesia)

Evidence: From JAMA- Does this Patient Have Parkinson Disease?

Most sensitive tests:
Glabellar tap- negative likelihood ratio of 0.13
Difficulty with heel-toe walking: NLR 0.3

Most specific tests:
Tremor, rigidity and bradykinesia: PLR 2.2
Difficulty with heel-toe walking: PLR 2.9
Glabellar tap: PLR 4.5

Findings making Parkinson's disease very unlikely:
Cerebellar signs
Pyramidal signs
Cranial nerve palsies

Link:

Click here for abstract of JAMA paper quoted above

Ischemic limb

Today we discussed an approach to a patient with an ischemic limb. This may be subdivided into acute vs. chronic ischemia, as these present and are managed differently.

Chronic peripheral arterial disease

Occurs in patients with vascular risk factors; almost always accompanied by CAD and cerebrovascular disease

Usually affects 3 distinct areas:
Aortoiliac-weak/absent femoral pulse (and popliteal, DP)
Femoropopliteal- weak/absent popliteal pulse (and DP)
Peroneotibial - weak/absent dorsalis pedis

Symptoms: Claudication, arterial ulcers and their complications (usually on toes, heel)
Signs:
-Skin, hair, nail changes- definitely should look, but not very helpful when looked at from EBM standpoint
Wounds/sores/ulcers- very specific; classically punched-out ulcer without surrounding venous stasis changes
-Temperature: asymmetrically cool foot is not sensitive, but is quite specific for PAD
-Pulses: absent femoral pulse is highly specific, not sensitive. Any absence of femoral, popliteal, DP is sensitive (i.e. if there is no pulse abnormality at all, negative LR is 0.3). Presence of any pulse abnormality is reasonably specific (positive LR is 15)
-Bruits: Presence is specific, absence is not helpful (i.e. not very sensitive)
-Special tests:
Cap refill: should do, but not very helpful from EBM standpoint
Pallor on elevation, dependent rubor: Sensitive for femoropopliteal disease, not very specific.
Venous refill time (find a prominent foot vein, elevate the leg to at least 45 degrees for one minute then sit patient up and measure the time it takes for the vein to rise above the skin surface again)- over 20s is very specific, but not sensitive.

Investigations: Ankle-brachial index
1.3: non-compressible, calcified arteries
1.0-1.3: normal
0.4-0.9: moderate obstruction, often with claudication
less than 0.4: advanced ischemia
Others: Arterial dopplers, angiogram (CTA, conventional angiogram)

Therapy:
Non-pharmacologic: exercise, smoking cessationPharmacologic: evidence for clopidogrel from CAPRIE trial; soft evidence for pentoxifylline

Surgical: Stenting, revascularization

Acute limb ischemia:

Acute onset of P's: pain (esp. resting), pallor, pulselessness, parasthesia, paralysis.
Etiology- thrombotic vs. embolic.
If thrombotic, usually progression of atherosclerotic disease to critical point. Other possibilites include primary arterial disease (i.e. large vessel vasculitis), spontaneous arterial clot event (e.g. antiphospholipid antibody syndrome, myeloproliferative disorders, Bechet's, possibly hyperhomocysteinemia, others)
If embolic, cardioembolic is common- A-fib, akinetic LV

Therapy: Anticoagulation and urgent surgical intervention- open or endovascular.

Links:

Click here for JAMA: Does the Clinical Examination Predict Lower Extremity Peripheral Arterial Disease?

Click here for Archives of Internal Medicine: Physical examination and chronic lower-extremity ischemia: a critical review

Cellulitis and "Cellulitis"

Today we discussed an approach to cellulitis, and its mimickers. Some key points:

Cellulitis: acute, spreading pyogenic inflammation of dermis and subcutaneous tissue, sometimes complicating a wound, ulcer, or dermatosis. Lacks demarcation from uninvolved skin.

Erysipelas: superficial cellulitis with prominent lymphatic involvement, making peau d'orange appearance with raised border demarcated from uninvolved skin. Patients are often sicker.


Predisposing factors: saphenous vein harvesting, edema, mastectomy with lymph node dissection, liposuction, "skin popping" in IVDU

Source: portal of entry in skin (e.g. tinea pedis, ulcer)- by far most common; other possibilities include osteomyelitis, bacteremia.
Unusual sources: seawater (vibrio vulnificus), fresh water (aeromonas hydrophilia), fish (strep iniae)

Cellulitis in unusual areas:
Periorbital cellulitis: eyelid and periocular tissues anterior to orbital septum
Orbital: Involves extraocular muscles; predisposes to cavernous sinus thrombosis, decreased visual acuity.

Micro:
80% gram +ve (staph, strep), 20% gram -ve. Aspirates/swabs are not indicated (unless ulcer)
Broader coverage may be indicated in pts with DM2.
Blood cultures are indicated in lymphedema, buccal, periorbital, water exposure, chills or fever. Otherwise, bacteremia is rare (less than 4%).

Empiric treatment: Cefazolin or cephalexin. Other possibilities: cloxacillin, clindamycin, penicillin, amoxicillin-clavulin. May want broader coverage (e.g. gram -ve coverage) in diabetics

Ancillary measures: Elevation, immobilization. Interdigital dermatophytic infections should be treated (e.g. clotrimazole and miconazole), terbinafine, etc

Some cellulitis mimickers to consider (see link to paper below for more)
-stasis dermatitis (especially if bilateral)
-superficial thrombophlebitis (often with IV/catheter site)
-DVT
-contact dermatitis
-drug reaction (can be 'fixed'- i.e. single area)
-Sweet syndrome (neutrophilic dematosis- see previous post)
-gout (can cause erythema overlying joint- i.e. 'periarthritis')

Links:
Click here for excellent NEJM review of cellulitis that most of this post is based on
Click here for Annals of Internal Medicine review of cellulitis mimickers (common and uncommon)

Monoarthritis

Today we discussed acute monoarthritis. Some points about the general approach and specific causes:

First question: Is this really arthritis (i.e. is it articular)? Important because non-articular causes are completely different (edema, ligamentous, tendon injury, etc)

Articular: Pain with any range of motion, effusion, morning stiffness, jt line tenderness. If multiple areas involved, more likely articular
Non-articular: Pain with specific ranges of motion, none of above.

Common causes of acute mono or pauciarthritis:
Septic arthritis- S. aureus, N. gonorrhea, S. pneumo
Crystal- gout/CPPD
Seronegative arthritis- esp. reactive, IBD-associated
RA (mono-articular)
Sarcoidosis (often bilateral ankle)
Trauma (fracture, hemarthrosis)

Common causes of acute polyarticular arthritis:
Endocarditis
Viral (HBV, HIV, parvo)
Serum sickness (drug rxn)
RA
SLE
Lyme (may also be monoarticular)

Some general features of specific causes:

Septic arthritis:
Risk factors: age, diabetes mellitus, rheumatoid arthritis, joint surgery, hip or knee prosthesis, skin infection, HIV, IV drug use
Clinical features: Joint pain in ~85%, joint welling in ~80%, and fever in ~60%
There are no physical exam findings that reliably rule in or out septic arthritis according JAMA Rational Clinical Exam paper linked below
Joint aspirate:
WBC over 100,000- Positive LR 28
WBC over 25,000- Positive LR 2.9
WBC less than 25,000- Negative LR 0.32
PMN over 90%- Positive LR 3.4; Negative LR 0.34
Also send for Gram stain, C+S, crystals
Common organisms:
St. aureus, St. pneumo, N. gonorrheae, Gram neg bacilli
Empiric tx: vancomycin and ceftriaxone

Crystal arthritis:
NB- finding crystals does not rule out septic joint! Can present the same way with fever, high WBC.
Gout vs pseudogout:
Gout: needle-like crystals, negatively birefringent, 1st MTP/ankle/knee. Risk factors are hyperuricemia, obesity, culprit meds (HCTZ, low dose ASA, others)
CPPD: rhomboid crystals inside macrophages, often hemorrhagic synovial fluid, positively birefringent. Knee, wrist, other. Risk factors: hypercalcemia, hemochromatosis, CKD.

Gout therapy
Acutely: Options are NSAID/colchicine/intra-articular steroid/systemic steroid
NSAID: Not in CHF or renal failure
Colchicine: Works, but often limited by GI side effects
Steroid:
Intra-articular highly effective with 1-2 jts. Confirm the diagnosis first.
Systemic- Prednisone 30-50mg PO x 3-5d then stop. Works well, but side effects.

Chronically: if 3 or more attacks per years, consider allopurinol

Links:
Click here for CMAJ review of monoarthritis
Click here for JAMA: Does this Patient have Septic Arthritis?

IgA nephropathy

Today we discussed IgA nephropathy. A few key points:

For a general approach to renal failure, click here.

Some important parts of assessment
1. Previous creatinine
2. Hx: drugs, volume, systemic disease (lung, joint, skin, fever...)
3. Volume status assessment, assesment for dialysis indications
4. Urinalysis: blood, protein, casts, cells, eosinophils
5. Urine lytes, osmolality
6. U/S of abdo to r/o obstruction
7. Serology: ANA, anti-GBM, ANCA, C3, C4 (if appropriate)

IgA nephropathy is the most common form of primary glomerulonephritis in the world.
Henoch-Schonlein purpura is a vasculitis associated with IgA deposition and may be a "systemic" form of IgA nephropathy (often with purpura, abdominal pain, arthralgias). Other associated conditions are celiac disease, IBD, and many other autoimmune conditions, and HIV.

Most commonly presents in 20's or 30's, more common in men than women (~5:1)

Many pts with IgA nepphropathy are asymptomatic. Most common ways of coming to clinical attention are

1) microscopic hematuria or proteinuria, which may be intermittent or

2) episodes of macroscopic hematuria or cola-coloured urine, which are classically associated with upper respiratory tract infection (but not commonly).

Firm diagnosis can only be made with biopsy, but which patients need biopsy is controversial.

Course is highly variable, from totally benign to rapidly progressive renal failure.

Worse prognostic indicators are:
1) degree of proteinuria
2) HTN
3) males

Conservative tx is BP management, ACE-I or ARB, fish oil (some evidence).

Specific tx is for crescentic/rapidly decreasing GFR. Cyclophosphamide, chlorambucil, steroids.

Link:
Click here for a NEJM review of IgA nephropathy

Diarrhea and HIV

Today we discussed diarrhea in the setting of HIV.

As a general rule, whenever faced with a new (or worsened) problem in the setting of a pre-existing disease, a useful dichotomy is whether this new problem is related or unrelated to the underlying disease. Pts with underlying HIV are still "entitled" to have the more common causes of diarrhea (or any other presentation)

Diarrhea, weight loss, malnutrition, and wasting was interestingly one of the first described syndromes of what came to be known as AIDS in 1985; it was initially called "slim disease" by African populations, as this Lancet article describes

Clinically significant diarrhea occurs in about 50% of HIV-infected patients in North America. The majority of these patients have an identifyable enteric pathogen if extensive enough workup is done. There is a small subset of HIV patients with "HIV enteropathy", in whom there is no identifyable pathogen. This is likely due to the effect of HIV itself and inflammation involving the GI lymphatic tissue.

Diarrhea may be more characteristic of small bowel pathology (post-prandial, voluminous, associated with weight loss and malnutrition) or large bowel pathology (frequent, small volume, with possible blood and mucous, tenesmus).

One way to approach the MANY opportunistic and other causes of diarrhea is by CD4 count:

Any CD4 count:
Bacterial: C. Diff, salmonella, shigella, campylobacter
Mycobacterial: M. TB
Parasitic: strongyloides, cyclospora, isospora, entamoeba histolytica, giardia lamblia

CD4 below 200: all of above and
Histoplasma capsulatum
Coccidioides

CD4 below 100: all of above and
Cryptosporidium (shown above)
Microsporum
Leishmaniasis

CD4 below 50: all of above and
MAI
Cryptococcus
CMV

Treatment is generally targeted at the identified pathogen. See Table 3 in below paper for details on specific agents for each of above.
Non-specific treatments include anti-diarrheals, low fat diet, nutritional support, and avoidance of lactose

Link:
Click here for a 2009 review from Gastroenterology on HIV and diarrhea (need journal access)

Fever and rash, Sweet's syndrome

Today we discused an approach to the patient presenting with fever and rash, some of the causes of a diffuse erythematous rash (i.e. erythroderma), and the more specific entity of "Sweet's syndrome"

Fever and rash- a broad differential needs to be considered, some of which are life-threatening and require immediate attention.

One possible way to approach this is by the type of rash involved, then subdivide by etiology (not intended to be complete):

Petechiae/purpura
Infections: Bacteremias (esp. meningoccemia, endocarditis), viral, rickettsial diseases.
Drug reactions (esp. septra, NSAIDs, b-lactam antibiotics)
Inflammatory: Vasculitis, autoimmune conditions (SLE, cryoglobulinemia, sjogren's, RA, many others)

Vescicular/bullous
Infections: Disseminated herpes zoster, disseminated herpes simplex
Drug reactions (Stevens Johnson, toxic epidermal necrolysis)

Macules/papules
Viral exanthem (think of parvo, HIV, HCV, EBV, others)
Syphillis (secondary); esp. hands and feet
Drug reaction (erythema multiforme, others)
Neoplastic: if fever-associated, hematologic malignancy more likely


Erythroderma- defined as 90% of body surface involved with erythema, swelling, scale. This narrows the differential somewhat; major causes include
Psoriasis
Cutaneous T-cell lymphoma
Sweet's syndrome
Drugs (esp. anticonvulsants, allopurinol, hydralazine)
Toxic shock syndrome

Sweet syndrome (shown above)- acute neutrophilic dermatosis
Papules coalescing into plaques. Erythematous, tender, on face, back, arms. May see fever, arthritis, conjunctivitis. 10% of these pts have malignancy, often AML. Other associations include infections (esp viral), autoimmune conditions, drugs.

Treatment usually includes steroids.

Wallenberg's syndrome

Today we discussed stroke in general, central vs. peripheral vertigo, and specifically the lateral medullary syndrome (i.e. Wallenberg's)

Vertigo- Central (brainstem, cerebellum) vs. Peripheral (inner ear)

Central:

Nystagmus is often bidirectional, sometimes vertical

Visual fixation makes no difference in symptoms

Vertigo may be chronic and often not severe

Cranial nerve deficits are common

Ear symptoms are absent

Peripheral:
Nystagmus is horizontal, often unidirectional

Visual fixation may improve symptoms

Vertigo is often severe

Head position often clearly exacerbates

No associated cranial nerve deficits

Often assoicated ear symptoms (deafness, tinnitus, otalgia)

Differential diagnosis of stroke -i.e. acute onset focal neurological deficit(s)
Seizure, dissection (esp young pt), migraine, demyelination, vasculitis. Any underlying brain abnormality with something that can cause delirium can cause focal findings (inc. infection, metabolic disturbances)

Lateral medullary stroke:
Results from occlusion of the ipsilateral vertebral artery (thrombotic, embolic, dissection), or a branch, the posterior inferior cerebellar artery.

Possible findings ipsilateral to lesion:
Pain, numbness of half of face (V1-V3)- 5th nerve nucleus
Ataxia, falling towards side of lesion- spinocerebellar tract, cerebellar peduncle
Nystagmus, diplopia, vertigo, nausea and vomiting- ipsilateral vestibular (8th nerve) nucleus
Horner's syndrome- ptosis, miosis, anhydrosis- sympathetic chain
Dysphagia, hoarseness- 9th and 10th nerve nuclei
Facial weakness (usually lower motor neuron type if 7th nerve nucleus involved)

Possible findings contralateral to lesion
Impaired sensation over half of body- spinothalamic tract
Limb power usually not involved because is more medial medullary (pyramidal tract)

Others: Intractable hiccups

Link:

Click here for a NEJM review of vertebrobasilar disease that includes a discussion of the lateral medullary syndrome

Falls in the elderly

Today we discussed the common problem of falls in the elderly. A few points:

May broadly approach causes for falls as "intrinsic" or "internal" vs "extrinsic" problem:

1) Exernal- overwhelming external hazards. Applies to anyone- surface (e.g. ice), tripping over surfaces, stairs, inadequate lighting, etc. Of course, the elderly may be less able to compensate for external hazards.

2) Internal- May be thought of like a computer (analogy courtesy of Dr. Ed Etchells)
Subdivided into: inputs, processing, and outputs, and power for the system

Inputs: vision, proprioception, vestibular apparatus
Therefore, problems with acuity, peripheral neuropathy, dorsal column pathology, inner ear pathology

Processing: cognition, basal ganglia, cerebellum
Therefore, primary CNS problems including dementia, Parkinson's, any cerebellar pathology

Output: Spinal cord, peripheral nerves, neuromuscular junction, muscle power.

Need adequate power to above system:
Cerebral blood flow, therefore arrhythmias, hypotension (inc postural), seizures.
Drugs: esp benzos (odds ratio of falling=30), but anything that causes postural hypotension (or hypotension in general), or any CNS depressant
Postural hypotension (need to check for it)

It may also be useful to divide falls into
1) isolated vs. chronic (look for acute medical issue in isolated)
2) with vs. without syncope (syncope involves a whole other differential)

Link:

Click here for a review paper on falls in the elderly, with references to evidence-based interventions to prevent falls and minimize morbidity from them

Dermatomyositis

Diagnostic criteria:
1) Proximal muscle weakness (shoulders, pelvic girdle muscles)
2) Increased CK
3) Myopathic changes on EMG
4) Muscle biopsy showing inflammation
5) Dermatologic involvement as outlined below

#5 + 3 others: Definite
#5 + 2 others: Probable
#5 + 1 other: Possible

Presentation:
Usually insidious onset of proximal weakness affecting shoulders, pelvic girdle. Neck flexor weakness also prominent. Dysphagia/dysphonia may occur. Synovitis is rare.
Pulmonary involvement with fibrosis/pneumonitis may occur. Cardiac involvement (myocarditis) occurs, but is relatively uncommon

Dermatologic findings:
Gottron's papules are lacy, pink/violaceous, raised or macular, and symmetric over dorsal IP jts, elbows, knees.
Heliotrope rash is violaceous discolouration of lids with periorbital edema.
Erythema of shoulders/neck (Shawl sign) or neck/chest (V-sign)- shown above
Periungal telangiectasias, nail changes (cuticular hypertrophy)
Raynaud's may be present
Mechanic's hands- coarse, fissured, scaly, hyperkeratotic hands

Investigations:
CK is increased during disease course, but not necessarily early. ASL/ALT/LDH may all be increased. ESR is >50 in 20%, normal in 50%.
EMG shows characteristic (but not pathognemonic) changes. Bx shows focal infiltration, CD8 T cells

Therapy usually consists of steroids, and possible addition of steroid-sparing agents such as methotrexate or azathioprine.

Malignancy association:
20-30% of patients have an underlying malignancy; dermatomyositis may pre-date the malignancy as in other paraneoplastic syndromes
It is controversial how aggressively to search for malignancy, and there is little high quality evidence to guide.
At the very least, everyone should get age-appropriate screening. Many experts would also measure tumor marker levels, and consider additional screening such as thoracic or abdominal imaging.

Link:
Click here for a good online review of dermatomyositis from American Family Physician

Churg-Strauss syndrome

Today we discussed Churg-Strauss syndrome, and some "tangents" related to it. A few concepts that came up:

Anatomic approach to weakness and associated features

Motor cortex: Upper motor neuron, involvement follows vascular territory. May see associated cortical findings (e.g. aphasia, apraxia, neglect, field defect). Usually unilateral

Internal capsule: Usually pure motor, with arm, leg, and possibly facial involvement. Unilateral. No cortical findings.

Brainstem: Crossed motor and sensory findings (i.e. lateralization of face and body may be different). Associated cranial nerve findings, level of consciousness may be affected

Spinal cord: Usually bilateral, often with a motor or sensory level.

Nerve root: Radiculopathy, usu at 1 level, often painful. Unilateral if physical compression If demyelinating (e.g. Guillain-Barre), bilateral leg weakness with areflexia

Peripheral nerve: Sensory findings associated, in dermatomal distribution. If general peripheral neuropathy, often length-dependent ("glove-stocking"), bilateral. If single nerves, this is "mononeuritis multiplex" or compression neuropathy.

Neuromuscular junction: No sensory findings, sometimes respiratory muscle involvement, with ptosis. Fatiguable if myesthenia gravis.

Myopathy: Bilateral, symmetrical, proximal. Sometimes CK elevation

Generalized: Think about metabolic abnormalities in addition to above (esp. PO4, K, Ca)

Mononeuritis multiplex differential diagnosis:
Essentially diabetes-related vs. vasculitis.
Common nerves involved in DM2: CN III, IV, VI, median nerve, peroneal nerve
Vasculitides that commonly cause mononeuritis multiplex: Churg-Strauss, polyarteritis nodosa, rheumatoid arthritis with vasculitic component

Eosinophilia Ddx
-parasitic infections
-allergic (asthma, allergy, eczema, AIN)
-vasculitic (Churg-Strauss, PAN)
-adrenal insufficiency
-hypereosinophilic syndrome (subset of hematologic malignancy; cardiac, CNS involvement)
-neoplastic (Hodgkin's lymphoma, CML, others)
-idiosyncratic drug reaction (common culprits are phenytoin, hydralazine, TMP/SMX, many others)
-cholesterol emboli

Churg-Strauss vasculitis

Click here for the American College of Rheumatology criteria for diagnosis

Asthma that is difficult to control is essentially an invariable feature of Churg-Strauss, and is one of the main differences between this and other similar vasculitides such as PAN and Wegener's granulomatosis.

Churg-Strauss should be suspected in patients with asthma (esp. adult onset) AND other organ involvement neurologic (esp. mononeuritis multiplex), gastrointestinal, pulmonary infiltrates, cardiac involvement (which would portend a poor prognosis), with eosinophilia.

Renal failure and glomerulonephritis is reported but less common than in other similar vasculitides (Wegner's, PAN)

Diagnosis is made by biopsy of affected organ or enough clinical criteria. 50% of patients have positive p-ANCA.

Treatment consists of high dose steroids and cytotoxic agents in high risk patients.

Link:

Click here for an excellent review of Churg-Strauss syndrome from Lancet

Nephrotic syndrome

Triad of hypoalbuminemia, edema, nephrotic-range proteinuria (over 3.5g/24h)
Other components of the syndrome: hyperlipidemia, hypercoagulability, lipiduria (causing oval fat bodies seen above)

The primary problem in the nephrotic syndrome is urinary protein loss due to altered permeability of the glomerulus. Other manifestations are all secondary to protein loss.

Loss of albumin and consequent loss of oncotic pressure lead to the clinical manifestation of edema, which may be profound. Periorbital edema is sometimes more prominent in the nephrotic syndrome than other causes of edema.

Hyperlipidemia results from urinary loss of regulatory lipoproteins, and low oncotic pressure may increase hepatic lipogenesis

Hypercoagulability may be arterial or venous, and often involves the kidneys themselves (i.e. renal vein thrombosis). May result from urinary loss of proteins c and s, and possibly antithrombin III

Causes in adults:

Primary renal diseases:
Minimal change
Focal segmental glomerulosclerosis (FSGS)
Collapsing glomerulopathy
Membranous nephropathy
Membranoproliferative GN (MPGN)
IgA nephropathy

Systemic diseases:
Infectious: HBV, HCV, HIV, syphillis, schistosomiaisis, malaria
Inflammatory/rheumatologic: SLE, amyloidosis, cryoglobulinemia
Malignancy: solid tumors, primary hematologic malignancies (e.g. Hodgkin's lymphoma)
Others: Sickle cell disease, heroin, drugs (e.g. gold, penicillamine)

Therapy:
1) treat the underlying cause
2) measures to limit proteinuria- largely ACE-inhibitors and/or ARBs
3) measures to deal with complications- salt restriction, careful diuretic use (as may become easily intravascularly depleted), statins, vitamin D supplementation if deficient

Links:

Click here for a NEJM clinical case on nephrotic syndrome