Pulmonary renal syndrome

In rheumatology morning report today we discussed an older woman presenting with hemoptysis and acute kidney injury with a Cr in the 700s. This lead to an interesting discussion of the many systemic disorders that can present with renal and pulmonary manifestations.

Pulmonary renal syndrome is essentially the simultaneous occurrence of both glomerulonephritis and diffuse alveolar hemorrhage. This usually manifests as a rapidly rising Cr, hematuria, and shortness of breath/cough/hemoptysis/desaturation. However, we must also remember that other conditions may cause acute kidney injury and pulmonary manifestations as well (ie acute kidney injury from prerenal failure or ATN complicating pneumonia, ARDS/AKI from sepsis/trauma, malaria, rapidly progressing AKI in CHF, etc). What really is needed to differentiate these entitities from true pulmonary renal syndrome is the presence of alveolar hemorrhage on bronchoscopy and the presence of glomerulonephritis on biopsy or urine microscopy (hematuria, red cell casts).

The causes of pulmonary renal syndrome include:

Connective Tissue Disorders

Polymyositis or dermatomyositis

Progressive systemic sclerosis

RA

SLE

Anti-glomerular basement membrane disease

Goodpasture's syndrome

Systemic Vasculitidies

Behçet's syndrome

Churg-Strauss syndrome

Cryoglobulinemia

Henoch-Schönlein purpura

Microscopic polyarteritis

Wegener's granulomatosis

Other

Drug Reactions

We discussed that the initial workup for these patients should include CBC + diff (for cytopenias), smear (for hemolysis), Cr, BUN, Lytes, Ca, Mg, PO4, albumin, LFTs, INR, PTT, CXR, EKG, and urinalysis and microscopy.

Further serology should include:

ANA, dsDNA if ANA positive (for SLE)

ANCA (c-ANCA (anti-PR3) positive in Wegener's, p-ANCA (Anti-MPO) in microscopic polyangiits, P>C-ANCA in Churg-Strauss. (Note: immunofluorescence is sensitive but less specific while ELISA is specific and sensitive. Know which one your lab does.)

Anti-GBM for Goodpasture's

Definitive Diagnosis: biopsy of lung/kidneys.

It is often necessary to make quick but definitive diagnoses as the consequences of not treating are dire, but the side effects of many of our immunosuppressive agents are not insignificant.

Please see a post from July on an interesting case of levimasole-induced vasculitis.

See here for an interesting review of ANCA vasculitidies from 2009.

Varicella & Pregnancy

Last week we discussed a case of an immunosuppressed woman with herpes zoster infection of the face, and the concerns that go along with that (what to do with her immunosuppressive medications? Ophthalmalogic concerns? Differential diagnosis). Today, we discussed a woman visiting from sub-Saharan African with a diffuse vesicular rash, ultimately thought to be disseminated varicella with varicella pneumonia. A surprise to everyone - someone wisely ordered a BHCG and she was, in fact, pregnant.

The CDC "Pink Book" has a wealth of information on many vaccine preventable illnesses - easily found by googling "CDC Pink Book". Looking under varicella, there is access to pictures, literature, vaccine recommendations, and more. Here is the link.

Varicella zoster virus (VZV) is a member of the herpesviridae family responsible for both acute infection ("chickenpox") and recurrent infection (herpes zoster, or "shingles"). After primary infection, VZV persists in sensory nerve ganglia and can result in recurrent infection, especially in immunocompromised hosts. It is transmitted through the respiratory tract (airborne & contact precautions in most hospitals!) with an incubation period of 14-16 days, although longer in immunocompromised hosts. Primary infection, as in our patient, is usually preceded by a 1-2 day malaise, followed by a generalized, pruritic rash that progresses from macules, to papules, to vesicular lesions, then crusts. Lesions of all ages can be found. Recurrent infection is more common in those with immunosuppression, advanced age, intrauterine VZV exposure, and VZV infection at less than 18 months. Zoster can become disseminated and involve the skin, CNS, lungs, and liver. It typically involves the fifth cranial nerve (as in our patient last week) or the trunk.

Complications can be severe, and can include:

• Secondary bacterial infection of skin lesions
• Viral or secondary bacterial pneumonia
• Meningitis or encephalitis (especially affecting cerebellum, leading to ataxia)
• Reye syndrome
• Myocarditis, GN, Transverse Myelitis, TTP, adrenal insufficiency
• Congenital Varicella Syndrome (CVS)

Congenital Varicella Syndrome is a risk if infection occurs in the first 20 weeks of gestation. Risk is actually pretty low (2%). It is manifest by:

• Low birth weight
• Hypoplasia of an extremity
• Skin scarring
• Localized muscular atrophy
• Encephalitis, cortical atrophy, chorioretinitis, and microcephaly

CVS is distinct from the risks if mum develops VZV from 5 days before to 2 days after delivery, which can result in overwhelming neonatal infection and 30% fatality rates. This is thought to be the result of fetal exposure without passive maternal antibodies.

We consider VZIg in certain populations, including:

• Immunocompromised patients
• Neonates whose mothers have signs and symptoms of varicella around the time of delivery
• Preterm infants born at or greater than 28 weeks gestation who are exposed during the neonatal period to non-immune mums
• Preterm infants born at less than 28 weeks' gestation or who weigh 1,000g or less at birth and were exposed during the neonatal period, regardless of maternal history of varicella disease or vaccination
• Pregnant women within 96 h of exposure

A few final pearls:

• All pregnant women should receive treatment (ie with acyclovir). See here for an article on management of VZV in pregnancy.
• Don't forget to consider other possibilities: Measles? Coxsackie? Impetigo? See here for some pictures and a summary table.
• Lastly, we must remember that geography plays a large role in varicella immunity. Many immigrant and refugee populations come from tropical and subtropical climates, where varicella immunity is much LOWER than in temperate climates like ours. Thus, a pregnant mum hailing from Zambia is a lot less likely than one born in Toronto to be immune to VZV. Given the risks, we should perhaps be engaging in routine antenatal screening of women from tropical/subtropical zones and providing vaccination, as well as insuring that they have access to timely and appropriate antenatal/pre/postnatal care. There has been some study on this issue, and here's an example.

Low Back Pain

Today we discussed a common presentation but difficult dilemma: chronic low back pain, with new neurological symptoms. When do you know to investigate further? How do you manage complex pain? What are the red flags? What is an anatomical approach to neurological manifestations? We discussed many of these issues today. For the internist, it is often important to be able to differentiate inflammatory from mechanical back pain.

It's worthwhile discussing the differential diagnosis of back pain, which includes:

Mechanical

• MSK injury
• Degenerative discs & facet joints
• Anatomic anomalies (scoliosis, spondylolisthesis)

Neurological

• Disk herniation, with irritation of adjacent nerve roots
• Spinal stenosis

Non Mechanical Spinal

• Malignancy (primary or secondary) with or without cord compression
• Inflammatory: Ankylosing spondylitis (& other seronegative spondyloarthropathies), RA
• Infectious: osteomyelitis, epidural abscess

Visceral radiation (pelvic, kidney, GI tract, aorta)

Remember that there are several key elements to a thorough back examination:

Inspection: anteriorly (looking for alignment), posteriorly (looking for asymmetry, deformity, rashes, etc), and laterally (for kyphosis, lordosis). Also inspect their gait.

Range of motion: Assess flexion, extension, rotation, and lateral bend while standing, looking for limitation & pain. From the seated position, test rotation of the spine at the thoracolumbar region - limitation is an early indicator of inflammatory back pain.

Palpation: of spinous processes and paraspinal muscles for pain or spasm.

Special Tests: compression test (of SI joints) with patient on side, FABER test, Gaenslen's test, Book test with patient supine (pressure over both trochanters.

Other special tests to differentiate between mechanical and inflammatory back pain include the straight leg raise (positive in mechanical), femoral stretch test, the occiput to wall test, the Modified Schober, and the

A full neurological examination should accompany this exam, including a DRE to assess for sphincter tone if cord compression is suspected.

See here for an excellent BMJ review.

Mental Health, Incarceration, and COPD

Thanks to Dr. Sargeant for an interesting morning report today, allowing us to explore some of the more complex issues affecting our patients with mental health concerns, including their disproportionately high representation in the prison system. The causality of this relationship is complex, and often influenced by confounders like addiction, but ultimately we have to look at this as a matter of public policy and how Canada (and other nations around the world) have chosen to allocate resources. I found an interesting resource document (here) from the American Psychiatric Association that discusses some of the broader factors and implications of the relationship between mental illness and the criminal justice system. An article on the role played by addiction can be found here.

We also discussed the clinical examination for airway obstruction, focusing on Dr. Sharon Straus' practical approach outlined here. Essentially, the combination of (all three) 1) self reported COPD, 2) Forced expiratory time >9 seconds, and 3) wheeze on auscultation had a positive likelihood ration (see here for definition) of 59, essentially ruling in COPD. Patients with none of the three findings had a negative LR of 0.3, effectively ruling it out.