@Jonathan Edwards as always I very much appreciate your scientific analysis and input. Same also goes to everyone else who has commented & "liked" my posts
Interesting to hear this
@TrixieStix.
Nobody really knows the immunological basis of RP but the way it moves from place to place without any obvious autoantibodies suggests that it is quite likely to be purely T cell mediated, like psoriasis. I don't think we have any theoretical reasons for thinking that plaquenil is helpful for T cell based problems. It is chiefly used in lupus, which involves B cell inflammatory mechanisms. I doubt there is any hard evidence from actual clinic use but I have not looked at the literature.
Leflunomide was devised as an anti-T cell drug, even though it was marketed for RA, which turns out to be a B cell disease where T cells are involved as bystanders as far as we know. In RA responses are either quite clear cut or not at all and are usually obvious after 20mg daily for three months.
I found this information online that says it is "current" & "updated" and my rheumy is one of the listed editors. I'm curious if after reading this you would revise any of your comments?
"The etiology of relapsing polychondritis (RP) is unknown. Although few clues are evident, there appears to be a genetic susceptibility, an overlap with other disorders associated with immunologic abnormalities, and the potential for multiple inciting events including chemical insults. This hypothesis is supported by a series of observations which imply that RP is not a primary disease but a syndrome associated with multiple precipitating factors that appear in a genetically susceptible subject. The paraneoplastic myelodysplastic relationship suggests a potential pathophysiologic role for clonally expressed lymphoid stem cells in which functional T cell defects induce both autoimmunity and uncontrolled neoplastic hematopoietic clonal proliferation. However, a report of abrupt onset after recreational drug abuse implies that a direct biochemical insult also can induce the disease."
https://www.uptodate.com/contents/e...lychondritis?topicRef=5587&source=see_link#H1
The following is also in the article, but this portion is only accessible with an account...
"PATHOGENESIS — Although the inciting cause may vary, increasing evidence derived from human and experimental animal studies has clearly implicated genetically preconditioned phlogistic and immunologic mechanisms that disturb connective tissue structure and cell function. In addition to the association with human leukocyte antigen (HLA)-DR4, the following observations are consistent with this hypothesis:
●The presence of autoimmunity, both antibody and cell-mediated, to extracellular matrix components of cartilage such as types II, IX and XI collagen, matrilin-1, and proteoglycan constituent fractions [
10-12].
●Some observations support the contribution of a cell-mediated immune reaction to type II collagen [
13]. As an example, T cell clones isolated from a DRB1*0101/0401 heterozygous patient with relapsing polychondritis (RP) showed specificity to a peptide derived from type II collagen that is an immunodominant epitope in a transgenic mouse model with features of RP. Of further interest are differences found in the epitope specificity for type II collagen antibody identified in patients with rheumatoid arthritis versus RP. Response in the rheumatoid patients was directed to an evolutionary conserved type II collagen domain that is also targeted by pathogenic autoimmune responses in murine models of arthritis but not RPC [
14].
●The prominence of HLA-DR-positive antigen-presenting cells and CD4-positive T lymphocytes at lesional sites [
15].
●Cartilage destruction may also be mediated by induction of apoptosis in chondrocytes. Chondrocyte expression of matrix metalloproteinase (MMP)–3 and cathepsin-K is strongly associated with this finding [
16].
●The genetically governed experimental induction of features of RP following immunization of experimental animals with connective tissue antigens. (See
'Genetic predisposition in experimental models' below.)
●Selective decreases in the number and function of natural killer regulatory T cells (NKT cells), a novel lymphocyte lineage distinct from conventional T, B, or NK cells which are believed to be involved in control of expression of autoimmune disease by modulating the balance of cytokine expression [
17].
Findings such as these have led to the generation of a unifying hypothesis which takes into account genetic predisposition, the immunogenicity of cartilage, and specific immunologic pathways important in mediating the disease process."
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In regards to Plaquenil, I know that many other people with RP are also taking it, and I believe this may be due to the fact that with RP often comes other autoimmune issues. In my case biopsies show that I have severe Small Fiber Neuropathy (so much so that I have developed significant muscle weakness in my left leg that affects my ability to walk uphill and stairs). It is my understanding that SFN is not a symptom thought to be caused by RP. I also have significant sicca symptoms (decreased tear production & dry mouth) so I seem to also be experiencing Sjogren's-like symptoms (I am seronegative & not had a lip biopsy). It's my hope that if this is the case that the Plaquenil will perhaps slow down or stop further progression of the SFN. I will try and remember to ask my rheumy the question "why I am taking Plaquenil?" at my next appointment.
I also have the whole genetic Complement deficiency thing as well and not sure how or if it may also be adding to my issues?
As for the sun sensitivity, it actually started last summer (it's when I first noticed it) which is before I was on any of these recent medications. Last summer I began to notice that my fatigue, joint pain, and malaise would worsen in the hours/days after any considerable time in the sun. And my skin also began to get red, blotchy and painful like I had gotten a sun burn even with very brief exposures to the sun.
Since I posted my update the other day I've had my most significant "flare" of my RP symptoms since beginning the Leflunomide. I remain hopeful as it's only been 1 month since I began taking 20mg daily. Fingers crossed I see a clear difference over the next 2 months. If not it will be on to the next drug.
