Multiple clinical manifestations of IgG4 related disease (IgG4-RD)

Here are some key issues addressed in a recent review.

What are some of the IgG4 related diseases?

These may coexist in the same patient:

Autoimmune pancreatitis type 1

Mikulicz disease (salivary gland infiltration)

Constrictive pericarditis

Coronary artery aneurysm

Inflammatory abdominal aortic aneurysm (and the related condition retroperitoneal fibrosis)

Sclerosing mediastinitis

Riedel's thyroiditis (and other forms of thyroid involvement)

Sclerosing mastitis

Pulmonary mass or interstitial disease

Hypophysitis

Prostatitis

Lymphadenopathy (Castleman like and other forms)

Tubulointerstitial nephritis

Sclerosing cholangitis (which differs in some features from primary sclerosing cholangitis)

How is IgG4-RD diagnosed?

This has been in a state of some controversy and flux. From the article:

According to an international symposium held in 2011, the diagnosis of IgG4-RD requires both an appropriate histological appearance and increased numbers of IgG4-positive plasma cells (or an elevated IgG4:IgG ratio) in tissue...

In 2011, an “All Japan IgG4 Team,” with the aim to draft comprehensive diagnostic criteria for IgG4-RD 51 ( Table 3 ), proposed three major items 51 69 (1) single or multiple organs involved with diffuse or localized swelling, masses, nodules, and/or hypertrophic lesions; (2) elevated serum IgG4 levels (greater than or equal to 135 mg/dL); and (3) histopathologic features that include marked lymphocytic and plasma cell infiltration and fibrosis, with IgG4-positive plasma cell infiltration (IgG4/IgG-positive cell ratio of greater than or equal to 40% and IgG4-positive plasma cells exceeding 10/HPF). Based on these criteria, patients can be classified into the categories of definite, probable, or possible IgG4-RD.

How do autoimmune pancreatitis (AP) types 1 and 2 differ?

Age: older onset (6^th decade) typical of type 1

Gender: male predominance in type 1, not 2

Relationship to IgG4: present in type 1, not clearly present in 2

Histology: lymphoplasmacytic sclerosing pancreatitis in type 1, idiopathic duct centric pancreatitis in 2

Abdominal pain: common in type 2, not in 1

Other organ involvement common in 1, not 2

Steroid responsiveness characterizes both types but type 1 is more prone to relapse.

IgG-4 related disease overview

Here is an overview from Disease of the Month. IgG-4 diseases include one of the two types of autoimmune pancreatitis and several other conditions:

Immunoglobulin G4-related disease is a rare but increasingly recognized multisystem entity characterized by lymphoplasmacytic tissue infiltration...Related manifestations of this disease include Reidel’s thyroiditis, chronic sclerosing dacryoadenitis, autoimmune pancreatitis (type 1 AIP), retroperitoneal fibrosis, and tubulointerstitial nephritis. Usually occurring in older men, the diagnosis is primarily based upon finding of histopahtologic changes..

High flow nasal cannula vs NIPPV post extubation

From a recent report in JAMA:

Question Is high-flow nasal cannula noninferior to noninvasive ventilation for preventing reintubation and postextubation respiratory failure?

Findings In this multicenter randomized noninferiority clinical trial that included 604 adults, the proportion requiring reintubation was 22.8% with high-flow therapy vs 19.1% with noninvasive ventilation, and postextubation respiratory failure was observed in 26.9% with high-flow therapy vs 39.8% with noninvasive ventilation, reaching the noninferiority threshold.

Meaning High-flow nasal cannula immediately after scheduled extubation was not inferior to noninvasive mechanical ventilation for risk of reintubation and postextubation respiratory failure in patients at high risk of reintubation.

Epilepsy driving laws by state

Here is the database from the epilepsy foundation.

Cystic lung disease as a manifestation of Sjogren Syndrome

From a recent paper in Chest:

Methods Eighty-four patients with primary or secondary SS and chest imaging, chest radiograph, or CT scan were retrospectively evaluated for CLD. Thirteen patients with cysts were found. Baseline characteristics of all patients were collected. A multivariate logistic regression model was used to look for predictors of CLD in patients with CT scan. Additional imaging, SS activity, and complications from CLD and SS were collected for the patients with cysts.

Results CLD had a frequency of 15.4% for all patients with chest imaging. Not all cysts were evident on radiography, and CLD frequency was 30.9% for the patients with chest CT scan. Six patients had cysts without other radiographic findings. CLD was associated with older age (OR, 1.1; 95% CI, 1.0-1.16), a diagnosis of secondary SS (OR, 12.1; 95% CI, 1.12-130.4), and seropositivity for anti-SS-related antigen A/Ro autoantibodies (OR, 26.9; 95% CI, 1.44-93.61). There was no radiologic progression of CLD for 12 patients after a 4-year median follow-up. Lung function did not exhibit temporal worsening. CLD did not correlate with a specific pattern in pulmonary function testing. Two patients had secondary infectious complications of the cysts.

And here is a nice general review of cystic lung disease and its various associations.

Cardiac imaging in pulmonary hypertension

Review here.

Viral infection in community acquired pneumonia

From a recent systematic review and meta-analysis:

Abstract:
The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP). Several studies have used PCR to establish the importance of viruses in the aetiology of CAP.



We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detected via PCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality.



Our review included 31 studies. Most obtained PCR via nasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5–27.5%). In studies that obtained lower respiratory samples in greater than 50% of patients, the proportion was 44.2% (95% CI 35.1–53.3%). The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32–3.31).



Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection.

PE may be hiding out in patients with COPD exacerbation

From a recent systematic review and meta-analysis:

Background COPD patients encounter episodes of increased inflammation, so-called acute exacerbations of COPD (AE-COPD). In 30% of AE-COPD no clear etiology is found. Since there is a well-known crosstalk between inflammation and thrombosis, the objectives of this study were to determine the prevalence, embolus localization and clinical relevance, and clinical markers of pulmonary embolism (PE) in unexplained AE-COPD.
Methods A systematic search was performed using MEDLINE and EMBASE platforms from 1974 – October 2015. Prospective- and cross-sectional studies that included patients with an AE-COPD and used pulmonary CT-angiography for diagnosis of PE were included.
Results The systematic search resulted in 1650 records. Main reports of 22 articles were reviewed and 7 studies were included. The pooled prevalence of PE in unexplained AE-COPD was 16.1% (95% confidence-interval 8.3%-25.8%) in a total of 880 patients. Sixty-eight percent of the emboli found were located in the main pulmonary arteries, lobar arteries or inter-lobar arteries. Mortality and length of hospital admission seem to be increased in patients with unexplained AE-COPD and PE. Pleuritic chest pain and cardiac failure were more frequently reported in patients with unexplained AE-COPD and PE. In contrast, signs of respiratory tract infection was less frequently related to PE.
Conclusions PE is frequently seen in unexplained AE-COPD. Two-thirds of emboli are found at localizations that have a clear indication for anticoagulant treatment. These findings merit clinical attention. PE should receive increased awareness in patients with unexplained AE-COPD, especially when pleuritic chest pain and signs of cardiac failure are present and no clear infectious origin can be identified.

The mechanism of the association, as pointed out in the abstract above, may be the association between inflammation and thrombosis.

Other factors were mentioned as possible mechanisms for the association, as pointed out in a review of the paper by ACP Hospitalist Weekly.

This is not the first time such an association has been mentioned, and I have blogged about it several times in the past including here.