11/7/17 Intern Morning Report – Lower Extremity Edema, Periorbital Swelling, Weight Gain, Nephrotic Syndrome, Diabetic Nephropathy

CC: Lower extremity swelling for 2 months

HPI: 32 year-old male with no known past medical history who presents with a chief complaint of lower extremity swelling for 2 months. Patient reports that he noticed swelling in his feet approximately 2 months prior to admission that has gradually worsened in severity. He now reports swelling extending to mid thighs that interferes with ability to ambulate comfortably, prompting him to present for evaluation. The swelling is not painful and without overlying skin discoloration and is symmetric bilaterally; he also states that his swelling is not firm but pits with digital pressure. He notes mild periorbital swelling over the past 3 weeks though he reports no visual disturbances.  On exam, patient has periorbital edema and pitting lower extremity edema to mid thigh but otherwise no other signficant findings.  Labs are significant for renal injury, non-gap acidosis, hyperkalemia, normocytic anemia, and UA>300 protein.  The urine protein/creatinine ratio is 13.84, high above the cut off for nephrotic range proteinuria.  Urine anion gap is positive. For work up of nephrotic syndrome, tests of ANA, SPEP/UPEP, Hepatitis panel, HIV, RPR, C3/C4, and HgbA1c were sent.  The only pertinent finding was a HgbA1c of 10.1.  A renal biopsy was pursued after ultrasound showed kidneys to be around 12cm in length with no other specific findings.  Biopsy demonstrated patient to have Kimmelstiel Wilson nodules which is consistent with Diabetic Nephropathy.


Morning Report Pearls:

Once you have nephrotic range proteinuria, remember the types of nephrotic syndromes. This will help organize how to evaluate for underlying etiologies. Some of these syndromes can be idiopathic but most have secondary causes.

  1. Membranous – Associated with Hepatitis B, Hepatitis C, Malaria, Syphilis, SLE, Medications, Malignancies (solid tumor and lymphoma), RA, and Sjogren’s
  2. Minimal Change – Associated with medications like NSAIDs, Malignancies (Hodgkin’s Lymphoma)
  3. FSGS – HIV, Obesity, Reflux Nephropathy, Sickle Cell, HTN, DM
  4. Amyloidosis
  5. Multiple Myeloma (Membranoproliferative possible finding)
  6. Diabetic
  7. IgA Nephropathy

Some basic screenings should be done based off this information: HIV, HgbA1c, ANA, C3/C4, Hepatitis B/C, SPEP/UPEP with Light chains

 

Be on the look out for complications related to Nephrotic Syndrome secondary to loss of albumin (drop in oncotic pressure) and other proteins:

  • Hyperlipidemia due to increase hepatic production of apolipoproteins due to loss of oncotic pressure and decrease lipoprotein lipase
  • Hypercoaguablility due to loss of Protein C, Antithrombin II and increase production of coagulation factors from decrease oncotic pressure. Note that renal vein thrombosis is most common in Membranous Nephropathy
  • Higher risk of infection due to loss of Immunoglobulins
  • Due to loss of carrier proteins some patients can become Vitamin D deficiency, Thyroid hormone deficient, Iron deficient

This patient had a non gap acidosis for which the differential is narrow:

  1. GI loss
  2. Renal Acidosis – RTA versus CKD
  3. Drug Induced

Given the hyperkalemia in the setting of lack of oliguria or insults with CKD, it was thought that patient had Type IV RTA. Here is a breakdown of the RTAs:

11/8/17 Resident Morning Report – Acute on Chronic Productive Cough, Shortness of Breath, Recurrent Rhinosinusitis, Bronchiectasis, Good Syndrome

CC: acute on chronic cough, shortness of breath for 1 week

HPI: 57 year old M with history of thymoma and chronic cough that presents with worsening cough and shortness of breath. Several months prior to presentation he developed a daily cough which is productive of yellowish green sputum. He was initially treated with omeprazole, loratadine, and fluticasone nasal spray, as well as nasal decongestants but had no improvement in symptoms. He also reports frequent rhinosinusitis infections, with productive nasal discharge and maxillary/frontal sinus pressure. These infections temporarily resolve with antibiotics from his primary care physician, yet they recur after several weeks. He presents to the ED now because his cough has worsened in regards to frequency throughout the day and in the amount of sputum production. In addition, he has developed worsening shortness of breath over the last week. He normally can ambulate multiple blocks but can now barely walk around his bedroom. Patient denies chest pain, fevers, chills, myalgias, night sweats, weight loss, or sick contacts.  Patient is found to be hypoxic to 89% on RA and to have bibasilar rales when auscultating lung fields.  Chest x-ray showed no consolidation but CT chest did demonstrate evidence of bronchiectasis which explained the patients acute on chronic symptoms. Sputum sample revealed patient to be infected with the encapsulated organism, H. influenza. Given the evidence of chronic rhinosinusitis infections, infection with encapsulated organism, bronchiectasis, and history of thymoma, a immunodeficiency work up was initiated.  Secondary immunodeficiency causes like diabetes, renal dysfunction, cirrhosis, HIV, and nephrotic syndrome returned negative. Patient’s work up revealed low immunoglobulin levels, low CD4 count which in the setting of a prior thymoma led to the diagnosis of Good Syndrome.  Patient has been treated with IVIG with decrease in infection frequency.

 

Labs:

Sputum Culture: H. Influenzae

HIV Ab/Ag negative

Flow Cytometry:  CD4 392, CD8 882, CD4/CD8 ratio 0.4

Tetanus Antibody Titer: <0.05 in the setting of vaccination within last year

Serum Immunoglobulins:
IgA     13   (79 – 455)

IgG     207 (650 – 1600)

IgM   < 3 (40 – 240)

IgE    < 2

HgbA1C: 5.8

UA: no protein

 


 

Morning Report Pearls:

Always go back to your basics when identifying types of immunodeficiencies:

  • Recurrent bronchi and sinus infections suggest an antibody deficiency = Humoral Immunodeficiency
  • Invasive bacterial infections tend to occur in the setting of complement defects and asplenia
  • Viral, fungal, and opportunistic infections are more prevalent in T cell deficiencies = Cell Medicated Immunodeficiencies
  • Skin Abscesses and deep tissue infection are concerning for innate immunity

Once you identify the area of immune system defect, you can focus the work up but always rule out secondary causes of immunodeficiencies first, as these are more common:

  • HIV
  • Nephrotic Syndrome
  • End stage renal disease
  • Cirrhosis
  • Malignancy
  • Malnutrition
  • Immunosuppressants

When the type of immunodeficiency is narrowed then further work up can be sought out.  In this case, patient had strong evidence in favor of antibody deficiency.  The work up consists of:

  • Immunoglobulin panel which will help with CVID or selective antibody deficiency diagnosis
  • IgG subset measurements are important when IgG is normal to diagnose IgG subclass deficiency
  • Test antibody function by evaluating antibody titers to protein and polysaccharides found in vaccines the patient has received

This patient was found to be deficient in all immunoglobulins and have low tetanus titers despite recent vaccination which went towards the diagnosis of antibody defect which can be seen in CVID.  However given the history of thymoma, Good Syndrome remained on the differential which involves also cell mediated defects.  This was confirmed by a low CD4 count.

 

 

 

 

 

11/3/17 Intern Morning Report – Joint pain, Fevers, Recent Diarrheal Illness, Oligoarthritis, HIV, Reactive Arthritis

CC: Joint Pain

HPI: This is a 32 year old male with history of chlamydia and new diagnosis of HIV who presents for painful joint swelling in bilateral knees and wrists for 5 days. He reports that approximately 3 weeks prior to admission, he experienced 1 week of abdominal pain, diarrhea, and fevers. While the GI symptoms resolved, he has had on and off fevers since. Five days prior to admission, he began to have bilateral wrist pain with swelling which then progressed to to his left knee followed by his right knee over the course of a few days. His social history is notable for being sexually active with both males and females with greater then 30 partners over the last few years.  His exam is pertinent for bilateral wrist and knee swelling, warmth and tenderness. There is difficulty ranging the joints with both passive and active motion.  Skin and lymph node exam is normal though.  Given history and exam consistent with an inflammatory oligoarthritis in the setting of recent gastrointestinal infection, reactive arthritis high on the differential but could not rule out disseminated gonococcal infection or atypical presentation of crystalopathy, septic joint, or rheumatoid arthritis.  Joint aspiration from wrist significant for a leukocyte count of >90,000 with >75% PMNs so patient initiated on antibiotic therapy for septic joint treatment.  However further studies on synovial fluid unrevealing including gram stain, culture, and crystals.  Serologies were also sent which showed a negative ANA, mildly elevated RF, and negative Anti-CCP.  Mucosal swabs for gonorrhea negative and though patient high risk, without other findings of disseminated gonococcal infection (DGI) like tenosynovitis, pustular rash, and migratory arthritis nor positive cultures from non-mucosal sites, DGI considered unlikely. With the clinical picture involving a recent diagnosis of HIV as well as a diarrheal illness in addition to negative infectious and crystallopathy work up, a diagnosis of reactive arthritis was made.

Some Notable Labs:

Wrist Synovial Fluid:
(H) 96,000 leukocytes/cumm
(H) 92 % PMNs

Gram stain and culture negative

  • CRP 170 (>7 high)
  • ESR 90 (0-22)
  • ANA Negative
  • RF: 58 (normal high 13)
  • Anti-CCP: <16
  • HLA B27 Positive

Right sided supra patellar effusion, otherwise normal X-rays.


Morning Report Pearls:

Though cases do not always fit the classic presentation, it can be useful to breakdown etiologies of joint complaints by the number involved.

Monoarthritis Differential

Oligoarthritis (2-4 joints) Differential

Polyarthritis (>5 joints) Differential

1. Acute Infection: Bacterial

2. Subacute/Chronic Infection: Fungal, TB, Lyme

3. Crystal Disease: CPPD, Gout

4. Osteoarthritis

5. Trauma

6. Monoarticular Rheumatoid Arthritis

1. Spondyloarthropathies: AS, Psoriatic arthritis, Reactive arthritis, IBD

2. Disseminated Gonococcal

3. Rheumatic Fever

4. Lyme Disease

5. Osteoarthritis

1. Chronic inflammatory: Rheumatoid arthritis, SLE, Psoriatic, Vasculitis

2. Acute Viral: Hepatitis, Parvo, Rubella, HIV, Enterovirus

3. Drug Induced Serum Sickness

 

 

Synovial Fluids Studies are important in differentiating non-inflammatory conditions from inflammatory. Also the degree of leukocyte elevation can provide useful information for determining an etiology.

Synovial Fluid Leukocyte Count:

<200 = Normal

200-2,000 = Non-Inflammatory

2,000 = Inflammatory

50,000 = High Concern for Septic Joint however Crystal Disease, Reactive Arthritis and other autoimmune disorders like Rheumatoid Arthritis can not be completely excluded

 

Mildly elevated Rheumatoid Factor occurs in the general healthy population and also be positive in certain infections and/or autoimmune conditions.  RF is very sensitive for the diagnosis of Rheumatoid Arthritis but that means it can include a higher number of false positives so mildly elevated results in the incorrect clinical picture needs to be scrutinized.  The fact that Anti-CCP is negative, a specific test, makes RA diagnosis less likely in this case as well.