Dr. Google: Possible reasons for low white blood cell count and and bruising easily?

While shopping for a dress yesterday I noticed a large bruise on my leg.  I do not even remember how I got it.  Then that made me ask "Doctor Google" what could make me bruise so easily and potentially be a cause for a low white blood cell count at the same time.  The potential reasons were many:

• Chediak-Higashi syndrome
• Hairy cell leukemia
• Hypersplenism
• Lupus

The first is a rare inherited immune condition so unlikely.  Hairy cell leukemia also comes with other symptoms like fever, weight loss, weakness, abdominal discomfort, so probably not the case.  Hypersplenism?  Well that could be due to beta thalassemia (inherited blood condition), chronic lymphocytic leukemia, malaria, TB, renal dialysis ... probably not... and also possibly due to rheumatoid disease (another name for rheumatoid arthritis?), connective tissue diseases, and inflammatory disease.  Lupus is probably not the case since the ANA test was negative.  Perhaps chronic gout could be the culprit, but the uric acid was normal.  For gout to be uncontrolled, the uric acid needs to be elevated enough to trigger the immune inflammatory response.  Gout is an inflammatory disease but so is rheumatoid arthritis.  There apparently is also a type of RA that would yield a negative result on the rheumatoid factor test and possibly the ANA test.  Most have positive RF so RA is possible but not likely at this point.  Psoriatic arthritis and ankylosing spondylitis could yield negative results on both the ANA and RF tests. 

Time will tell what the issue is, but it looks like some sort of inflammatory rheumatic condition that is slowly progressing.  And my spleen may not be so happy. Right now, I feel the best I have in weeks.  This week, my joints are not as sore and my fingers and thumbs not as stiff in the morning.  I still have the bursitis but went shopping for more than 2 hours yesterday and forgot I had it.  I wonder if this is what people call "remission".    

Chromosome 8: Rare and Uncommon Variants

A few uncommon variants were tested for by 23andme on Chromosome 8 that I found:

rs4994: ADRB1, MAF, G = 0.115, missense, susceptibility to having obesity, heart trouble, gout, and possibly other conditions according to SNPedia.

rs17368310: : PKHD1L1, MAF, C = 0.0545, splice donor variant.  The gene is associated with polycystic kidney and hepatic disease 1 (autosomal recessive).  Not sure if this variant would contribute to the condition.

rs10088218: LINC00824, MAF, A = 0.0867, intron variant.  Half the risk for ovarian cancer if AA according to SNPedia.

rs2705293: LOC401478, MAF, C = 0.1274, intron variant.  May contribute to neuroticism.

Psoriatic Arthritis and Gout?

Someone recently suggested that I look into the possibility of having psoriatic arthritis.  My first thought was that I do not have psoriasis, but I looked into it anyway.

I've had an ugly toe since high school, but thought it was a lifted nail bed from running cross country.  There's also a spot on my scalp that feels more flakey to the touch and has not gone away.  Never thought much about it.  Only one toe is "ugly" but those others so far are unaffected.  There is some genetic susceptibility to developing psoriasis.

rs1265181: CG, MAF = 0.101. Increased risk for developing psoriasis
rs1265159: POU5F1, AG, MAF, A = 0.1569. 5x risk for developing psoriasis

There also seems to be an association with psoriasis and psoriatic arthritis with the development of gout (read here).  I currently do not have high uric acid but had what appeared to be a gout attack in 2014.  I also have a lot of genetic susceptibility for developing gout due to the ABCG2 gene.  One interesting statement is, "For men and women with both psoriasis and psoriatic arthritis, the risk of developing gout was nearly five times greater compared to participants with no psoriasis or psoriatic arthritis."  I suppose having both psoriatic arthritis, an autoimmune disease, and gout, a crystal induced arthritis, is not so far-fetched after all.  Since my rheumatoid factor was negative, psoriatic arthritis is a possible cause for the polyarticular joint pain despite keeping my uric acid within the normal range.  PsA may fit the bill because:

• Lifted toenail, dry patch in scalp
• Bursitis in the right hip preceded the gout attack
• Low white blood cell count, which could be due to an inflammatory or autoimmune condition
• Rheumatoid factor was negative
• Genetic susceptibility for gout and psoriasis
• Was 31 when I develop polyarthritis
• Had gastrointestinal issues at one point
• Had a gout attack
• I still have more joints getting affected even after controlling my uric acid level
• Started having persistent lower back pain
• Could cause symmetrical or asymmetrical joint pain

Hip Bursitis Probably From Inflammatory Arthritis

After doing a little bit of online research, it looks like I have had hip bursitis since the fall of 2013.  Then the gout attack during February of 2014.  The only thing showing up in my blood work as of March 2018 is the low white blood cell count.  My uric acid level was well within the normal range.  Bursitis at my age could be due to an underlying inflammatory arthritic condition.  People normally do not get bursitis so young.  Could gout be causing this?  Or is this an early sign of a milder form of rheumatoid arthritis?  There is a such thing as seronegative rheumatoid arthritis, where the blood work is negative.  Polyarticular gout or rheumatoid arthritis brewing under the radar would be my guess as to what's going on with me since the hip bursitis never went away.  

Low White Blood Cell Count?

So far the only test result that could indicate that something is "up" is the low white blood cell count.  Fortunately, I had a checkup in September 2013, so I am able to compare my results to the time before my first gout attack.  I was already starting to have issues standing up for more than a few hours, but it was easier to ignore then.  After doing some reading on it, it is probably trochanteric bursitis.  The morning I saw the doctor I also seemed to have ischial bursitis, sharp pain when I sat down or got up.  My white blood cell count was 4.5 thousand/uL which was clearly within the normal range.  The neutrophils were 2714  cells/uL and the absolute monocytes 207 cells/uL.  In March 2018 the white blood cells count was 3.8 thousand/uL, neutrophils 2.0 thousand/uL and monocytes 0.2 thousand/uL.  So not very low, but enough to merit some investigation.  The monocytes were close to or below the normal range during both tests.

Low monocytes could be due to an inflammatory condition, autoimmune disease, infection, bone marrow issues, etc.  Low neutrophils could be due to bone marrow diseases, vitamin deficiencies like B12 or folate, infection, enlarged spleen, autoimmune diseases, medications such as antibiotics.  Someone suggested to me that my achy joints could be due to B12 deficiency.  I had that before, but the red blood cells are currently normal in size and quantity making that a little less likely.  I take a prenatal vitamin along with a B-complex pill here and there to prevent anemia.  I had a mild case of mastitis that resolved about 3 weeks before the blood test was done.  Maybe it was a simple as the counts not going up before the test was done.  I'll be sure to keep taking my vitamins and supplements, maybe more often now, and hope I don't get sick before getting tested again in August.

I write all this because it may end up shedding some light on some early signs of whatever it is that I have.  It could be gout, like the genetics suggest.  That's a lot of issues with bursitis if it is gout.  And with a uric acid level of only 4.6 mg/dL.  So what looks to be bursitis was my first symptom in 2013.

Rheumatoid Arthritis Risk Variants

Using Promethease, I took a quick look to see if I'm a carrier for any risk alleles for developing rheumatoid arthritis.  The following SNPs may be relevant:

rs7574865, STAT4 gene: Hetero = 1.3x risk for RA and higher risk for other autoimmune diseases. 

rs3738919, ITGAV: Homozygous CC = 1.94x for RA

rs6457617: Hetero = 2.3x risk for RA

rs2240340, PAD14: Homozygous AA = 1.3x risk for RA 

rs3766379, CD244: Homozygous TT = 1.9x risk for RA

rs6314, HTR2A: Heterozygous = Higher risk for RA

rs6313, HTR2A: Heterozygous = Higher risk for RA

rs6682654, CD244: Homozygous GG = 1.8x risk for RA

rs6910071, C6orf10, LOC101929163: Heterozygous, AG = possibly 4x risk for RA (due to the G allele, MAF = 0.1048)

rs660895: Heterozygous = possibly 4x risk for RA

rs2104286, IL2RA: Heterozygous = 1.4x risk for RA

rs6684865, MMEL1: Homozygous AA = 1.5x risk for RA

Another possibly relevant allele includes:

rs7454108: Heterozygous = Single HLA-DQ8 haplotype, DQ8 is commonly linked to autoimmune disease in the human population.  C is the risk allele with a MAF = 0.0798.

The 23andme raw data for an important gene relating to rheumatoid arthritis, HLA-DRB1, is not easy to decipher since it contains many proprietary markers (beginning with "i") such as i5033422.  Note that there are several genes involved with rheumatoid arthritis risk.  It's not easy to tell what the susceptibility is for any individual.  From what I can tell there also needs to be some sort of environmental trigger for an autoimmune disease, like rheumatoid arthritis, to develop.

I don't want to be a hypochondriac, but I remember getting pityriasis rosea in the winter of 2016 and diagnosed by a doctor in May 2016.  The herald patch appeared in February and in April and May the full blown rash developed.  I also remember being sick for 2 weeks around that time.  I had a miscarriage in April.  Then pregnant in June.  That was a hard year!  The polyarticular arthritis did not appear until October 2017 (about 7 months after my first child was born).  I thought it could be chronic gout, but the uric acid was low enough, to make me think it could be something else.  This morning I woke up with a new joint in my left thumb being sore and stiff.  The same joint of my right thumb has been affected since October.  Symmetrical joint pain could be a sign of RA.  Will keep you posted!

Rheumatoid Factor and ANA Negative! Yay!?

At first, I was ecstatic that my test results for rheumatoid factor and ANA were negative.  Meaning probably not rheumatoid arthritis nor lupus.  But I did not know about another type of inflammatory arthritis that could go undetected by the two tests.  Something called ankylosing spondylitis.  This usually starts in the lower back, specifically the sacroiliac joints.  Arthritis could present in other parts of the body.  There's also the possibility that I'm too early in the progression of whatever it is that's ailing me to show up in a blood test.  The doctor wants to see me again in August.  So the best thing I could do is just keep track of any major symptoms and let her know what's up.  So far the following since October 2017 developed arthritis:

• Right thumb
• Left thumb
• Finger stiffness in both hands
• Right hip gives out due to stiffness
• in the morning, especially the day after standing a low
• Left hip started giving out on March 17, 2018 after standing a lot 
• Burning pain in lower back after entertaining for a couple of days and throwing a birthday party.  Lots of cooking and standing involved.  Since the fall of 2013 the joints around my hip area started to get painful after only standing for 2 to 3 hours.  I still have the same problem.
• Lower back always sore.  I try to do stretches periodically to prevent stiffness.  My back can get really stiff after standing up a lot.

I searched my genetic data to see if I'm a carrier of any HLA-B27 alleles, which increase the risk for ankylosing spondylitis but did not find anything.  However, there are HLA-B27 alleles that are not tested by 23andme.  Since my late biological mother developed arthritis when she was relatively young (30s-40s), I'll keep an eye out for any symptoms that could indicate ankylosing spondylitis.  She did not have the means to get checked out for her arthritis so I'm not sure if it was due to not taking care of herself or if there was a hereditary component.  

I don't want to dwell on what's hurting all the time, but I'd like to know what it is in hopes of being able to treat it.  My dad seems to think that my issues are not normal for someone my age and presently the only person that seems to take what I'm going through seriously.  I'm glad I have at least one person that has sense enough to see that this is not normal and wants to get to the bottom of it too.

Chromosome 7: Rare and Uncommon Variants

I am in the process of scouring Chromosome 6 for susceptibility for rheumatoid arthritis, but in the meantime here is what I found in Chromosome 7.

rs17420802: MAF, C = 0.0004, PMS2.  Benign missense.

rs2032583: MAF, G = 0.1454, ABCB1.

rs10488631: MAF, C = 0.0591, TNPO3. Downstream variant 500B. Clinical Channel; 2x increased risk of developing Systemic Lupus Erythematosus (SLE); 1.6x increased risk of developing primary biliary cirrhosis; and 1.7x increased risk of developing Sjögren's syndrome.  So there is some susceptibility for developing an autoimmune condition from this one allele.

rs12531711: MAF, G = 0.054, TNPO3. Intron variant.

rs67047829: MAF, A = 0.1152, ERV3-1, ZNF117 .  Stop gained, upstream variant.

rs78655421: MAF, A = 0.0015, CFTR. Missense.  Pathogenic untested allele, for cystic fibrosis.  There are host of other CFTR mutations tested for by 23andme, which could be picked up running raw data using Promethease.  If I remember correctly, this particular variant does not have 100% penetrance.  Meaning that if one is homozygous for the minor allele, it does not always result in being affected with cystic fibrosis.