Other ctd's sj, igG4, pms, ery nod, Still

Question 1

IgG4 related disease (IgG4RD) may affect what systems?

Answer 1

IgG4RD may involve salivary and lacrimal glands, autoimmune pancreatitis, cholangitis, retroperitoneal fibrosis, aortitis and periaortitis, thyroid disease, lung and pleural disease, and renal disease.

Question 2

What is unique about IgG4 antibodies?

Answer 2

The disulfide bonds linking the heavy chains in IgG4 can link multiple molecules together and form unusual immune complexes. Levels of IgG4 above 135 mg percent occur in about 90% of patients with IgG4RD. 7.5% of primary sjogren’s syndrome patients have elevated IgG4 but only those with autoimmune cholangitis (AIC), autoimmune pancreatitis (AIP), or interstitial nephritis.

Question 3

What are the consensus criteria for diagnosis of Sjogren’s syndrome?

Answer 3

The American European consensus group definition for Sjogren’s syndrome includes:1. Ocular symptoms of inadequate tear production2. Ocular signs of formula damage due to inadequate tearing.3. Oral symptoms of decreased saliva production4. Salivary gland histopathology demonstrating foci of lymphocytes.5. Tests indicating impaired salivary gland function.6. SSA/anti-Ro, SSB/anti-La autoantibodies.

Question 4

What gastrointestinal symptoms can be attributed to Sjogren’s disease?

Answer 4

Sjogren’s syndrome often causes nausea, epigastric pain, and dyspepsia. Atrophic gastritis from CD4+ T cell infiltration can result in pernicious anemia. Celiac disease is increased similar to diabetes and autoimmune thyroid disease.

Question 5

What is different about HIV associated parotitis and Sjogren’s syndrome?

Answer 5

The infiltrate in HIV-associated disease consists of cytotoxic CD8 T cells, and Sjogren’s infiltrate are 75% helper CD4 T cells.

Question 6

What is the cause of dysfunctional tear syndrome?

Answer 6

Breakup of the mucus layer with subsequent decrease in goblet cell function, dryness and activation of metalloproteinases.

Question 7

What skin changes can occur in Sjogren’s syndrome?

Answer 7

Skin involvement in Sjogren’s syndrome can include xerosis, cutaneous vasculitis, Raynaud’s phenomenon, and annular erythema,

Question 8

What are the typical features of adult Still’s disease?

Answer 8

Still’s disease usually involves the knees, ankles, wrists more than the small joints and is often associated with pharyngitis, and lymphadenopathy. Biopsy shows B cell hyperplasia. Hemophagocytic syndrome is a rare complication and accounts for most deaths. Interstitial lung disease and myocarditis can happen. White cell counts over 15,000 and elevated ferritin levels are common. Biopsy of the skin rash shows complement deposition.

Question 9

What are the diagnostic criteria for adult Still’s disease.

Answer 9

The Yamaguchi criteria for adult Still’s disease include four major criteria:
1. fever at least 39°C
2. arthralgia or arthritis lasting two weeks or longer
3. nonpruritic skin rash which is maculopapular and salmon colored found on the trunk and extremities during febrile episodes
4. leukocytosis exceeding 10,000 with at least 80% granulocytes.
Minor criteria include sore throat, lymphadenopathy, hepatomegaly or splenomegaly, elevated AST or ALT, and negative testing for ANA and rheumatoid factor. Criteria are satisfied if at least 5 items are present including at least 2 major criteria

Question 10

What is unique about the histopathology of IgG4RD?

Answer 10

There is marked infiltration by plasma cells and lymphocytes with storiform fibrosis (spoke wheel distribution).Biopsy showing increase in IgG4 plasma cells are specific.

Question 11

What treatments work for IgG4RD?

Answer 11

Prednisone at 0.5 mg per kilogram for months with additional methotrexate, azathioprine, mycophenolate, or rituximab if necessary. There are no randomized controlled trials.

Question 12

What neurological changes occurring Sjogren’s syndrome?

Answer 12

Neurological problems include peripheral neuropathy, brain and spinal cord involvement, fatigue and fibromyalgia, depression and personality disorders.

Question 13

What pregnancy complications occur in Sjogren’s syndrome?

Answer 13

Pregnancy complications includeneonatal lupus and congenital heart block.

Question 14

Does relapsing polychondritis cause central nervous system disease?

Answer 14

Relapsing polychondritis may rarely affect the central nervous system causing aseptic meningitis, lymphocytic meningoencephalitis, rhomboencephalitis, limbic encephalitis, and pachymeningitis. Myelitis and peripheral neuropathy have also been reported. Up to one third have an additional form of systemic vasculitis, connective tissue disease, other autoimmune disorder, or malignant or premalignant condition.

Question 15

What additional membrane receptors occur on memory B cells infiltrating the salivary glands in Sjogren’s syndrome?

Answer 15

CXCR4+(CD184, stromal derived factor receptor causing chemotaxis, HIV receptor), CXCR5+(CD185, 7 transmembrane receptor for b cell mitogen), CD27+ (TNF receptor family, cd70, proliferation and Ig synthesis)

Question 16

What immune mechanisms cause glandular damage in Sjogren’s syndrome?

Answer 16

Perforin/granzyme A, FAS/FAS ligand (CD95/CD95L), cytokines, autoantibodies, metalloproteinases.

Question 17

What sort of CNS involvement may occur in IgG4RD?

Answer 17

There are five reported cases of IgG4RD associated with pachymeningitis,

Question 18

What is the course of IgA nephropathy?

Answer 18

IGA nephropathy refers to a common primary glomerulonephritis characterized by variable IGA deposition and pathogenic features including essential hypercellularity, segmental glomerular sclerosis, endocapillary hypercellularity, and tubular atrophy/interstitial fibrosis. It usually presents with proteinuria or hematuria and the prognosis is worse with increasing degrees of hypertension and proteinuria. Progression to renal failure usually takes decades. Treatment with ACE inhibitors or ARB’s is effective and if early in acute daily prednisone at 0.5 mg/kg seems to help test of addition of cyclophosphamide but not Azathioprine.

Question 19

What conditions are associated with IgA glomerular deposits?

Answer 19

Glomerular deposits of IGA also occur in cirrhosis, celiac disease, HIV infection, the normal change disease and membranous nephropathy, and granulomatosis with polyangiitis
Glomerular deposits are primarily IgA1 and J chain. these are indistinguishable from deposits in Henoch-Schonlein purpura.

Question 20

What mechanisms might cause urticaria?

Answer 20

urticaria usually due to IGE mediated antigen binding on the surface of mast cells, IgG antibodies to IGE are to its receptor induce intent to reaction. Circulating immune complexes may bind to mast cells with Fc receptors for IgG and IgM for a type III HS reaction. T cells they activate mast cells. Nonimmune mast cell activation can occur through compliment, toll like receptors, opioid receptors or by xenobiotics (haptens, drugs)

Question 21

What is the incidence of anaphylaxis?

Answer 21

The incidence of anaphylaxis by random telephone survey is estimated at 5.1% for probable and 1.6% for likely, or 30 per 100,000 person years. Food induced is the leading single cause in emergency rooms (15-57%). About 200 deaths per year occur due to food, and 50 from insect stings.

Question 22

How well does hydroxychloroquine prevent progression in Sjogren’s syndrome?

Answer 22

Hydroxychloroquine 200 mg bid did not improve fatigue, pain, IgG levels, SSA levels, or systemic involvement in a French controlled trial of 120 patients. 7/2014 PMID 25027140

Question 23

What other conditions are also associated with scleritis?

Answer 23

Scleritis is associated with systemic disease in 50% of cases, 40 % with a rheumatic disease, most commonly rheumatoid arthritis-vasculitis, but also with reactive arthritis, systemic lupus erythematosus, relapsing polychondritis, granulomatosis with polyangiitis, microscopic polyangiitis, Churg-Strauss syndrome, polyarteritis nodosa, Cogan syndrome, Sarcoidosis, inflammatory bowel disease, and Behcet’s syndrome. Infectious causes 8 %, include syphilis, tuberculosis, Lyme disease, herpes simplex and zoster.
Anatomical diagnoses include diffuse anterior sclera rightists, nodular anterior scleritis, necrotizing anterior scleritis. scleromalacia perforans, and posterior scleritis.