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A Thriller of Joint Ache: Is It Rheumatoid Arthritis (RA) or Hereditary Hemochromatosis (HH)?

A 58-year-old girl with a earlier prognosis of rheumatoid arthritis (RA) was referred to Rheumatology to handle her joint pains. On analysis, it was famous that the woman didn’t have any indicators of synovial irritation. The affected person had a destructive anti-cyclic citrullinated peptide (anti-CCP) (<0.5) and destructive rheumatoid issue (RF) (<10) along with excessive ferritin (1,507 µg/L) which led to consideration of hereditary hemochromatosis (HH) quite than RA. She was then referred to Hematology for normal venesection which settled her signs of it. This case report highlights the significance of contemplating HH as a differential prognosis in sufferers with persistent arthritis, significantly if there aren't any medical indicators and destructive assessments for RA. Extra retrospective research can be wanted to quantify what number of instances of hemochromatosis arthropathy have been mistakenly identified as RA.


Hereditary hemochromatosis (HH) is an autosomal recessive genetic dysfunction because of mutations of the homeostatic iron regulator (HFE) gene (situated on the quick arm of chromosome 6). It’s characterised by elevated intestinal iron absorption inflicting iron overload in inside organs [1]. It may well manifest in a number of organs together with joints inflicting arthropathy mimicking options of rheumatoid arthritis (RA). In roughly half of the instances of HH, persistent progressive arthritis affecting metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints and wrists is the presenting grievance and might typically perplex physicians and result in a prognosis of inflammatory arthritis [2].

Case Presentation

A 58-year-old girl was referred to the Rheumatology outpatient division by her Basic Practitioner (GP) because of growing ache within the neck and low again ache. She was beforehand identified as potential RA over 10 years in the past in one other hospital the place she was initially handled with methotrexate (MTX) which was later stopped because of unintended effects. We would not have any documentation concerning why and the way she was initially identified with RA. She denied any household historical past of psoriasis or inflammatory bowel illness.

On medical examination, her lumbar backbone motion was considerably restricted. No energetic synovitis was famous on MCP joints or interphalangeal joints of the fingers or wrists. determine one reveals an x-ray of her lumbar backbone which confirmed delicate scoliosis of the lumbar backbone convex to the left with the anomalous articulation of L5 and S1 on the suitable, marked intervertebral house narrowing at L3-L4 and reasonable disc house narrowing at L4-L5 . MRI lumbar backbone in determine 2 Confirmed no proof of current or historic vertebral fracturing however indicated L3/L4 and L4/L5 spondylotic adjustments with central high-grade stenosis with transiting neural impingement. figures 35 confirmed no abnormalities in fingers, elbows, and toes respectively.





The plan was made to revisit the earlier prognosis of inflammatory arthritis/RA as there have been no energetic inflammatory arthritis options. The opposite differentials could be seronegative arthritis or any systemic causes that would mimic RA comparable to polyarticular gout, or HH.

On biochemical investigations as proven in Desk one, her full blood depend was regular with an erythrocyte sedimentation fee (ESR) of two millimeters per hour (mL/hr), and C-reactive protein (CRP) 5 milligrams per liter (mg/L). Her de ella human leukocyte antibody B (HLA-B) 27, anti-nuclear Ab (ANA), anti-centromere Ab, anti-cyclic citrullinated peptide (anti-CCP) antibody, and rheumatoid issue (RF) had been destructive. The iron profile confirmed that Ferritin 1507 micrograms per liter (mcg/L), Iron 35 micromoles per liter (mcmol/L), transferrin 1.5 grams per liter (g/L), and transferrin saturation 93 % (%). A hemochromatosis gene display revealed that she is homozygous for the C282Y mutation leading to a tyrosine for cysteine ​​substitution at amino acid 282. She was referred to Hematology for weekly venesections. Her GP de ella was suggested to display her siblings and her husband de ella in view of her considerations about her youngsters being affected.

assessments outcomes models Regular vary
haemoglobin 140 Grams per liter (g/L) 115-165
white cell depend 5.5 109 per liters 4-11
Platelet 192 109 per liters 150-450
C-reactive protein 5 Milligrams per liter (mg/L) 0-7
Erythrocyte sedimentation fee 2 Millimeters per hour (ml/hr) 2-16
Anit-cyclic citrullinated peptide Antibody <0.5 kilo Worldwide models per liter(kIU/L) 0-2.9
Rheumatoid Issue <10 Kilo Worldwide models per liter (kIU/L) 0-14
Human leukocyte antigen B27 destructive
Anti-nuclear Antibody destructive
Anti-centromere Antibody <0.2 AI 0-0.9
ferritin 1507 Micrograms per liter (mcg/L) 10-150
Iron 35 Micromoles per liter (mcmol/L) 9-30
transferrin 1.5 Grams per liter (g/L) 2-3.6
Transferrin saturation 93 proportion (%) 15-45

In the course of the follow-up, she had been feeling a lot better. She had additionally been seen by gastroenterologists who organized an additional non-invasive liver display with the US scan of the stomach as proven in Determine 6. The liver seems mildly, and uniformly elevated in echogenicity in keeping with fatty infiltration. Liver elastography confirmed an elevated acoustic radiation power impulse (ARFI) studying of 1.88 meters per second(m/s) which signifies F2 fibrosis. Non-invasive liver screening blood confirmed destructive for gastric parietal cell antibody, liver kidney microsomal antibody, anti-mitochondrial antibody, and clean muscle antibody. On genetic screening, her siblings of ella and three youngsters (aged 25, 24, and 22) are famous to be carriers of the hemostatic iron regulator (HFE) gene.



HH, an autosomal recessive genetic situation, is the commonest reason for main iron overload, related to C282Y alleles [3]. Scientific shows of HH vary from bronze pores and skin to diabetes, cirrhosis, and hepatocellular carcinoma [4]. Nevertheless, it’s fascinating to notice that arthropathy is the commonest presenting grievance in sufferers with HH predating a few years earlier than the prognosis of HH [4]. Due to this fact, it isn’t shocking that it’s typically confused with different rheumatic illnesses together with Rheumatoid Arthritis (RA). In an identical case introduced by Ryan Hum and Pauline Ho [5]curiously, US fingers and toes confirmed energetic proof of synovitis explaining the affiliation of potential chondrocalcinosis related to HH [5]. HH arthropathy can current as typical hand osteoarthritis (HOA) presentation. Nevertheless, the latter would extra severely have an effect on the MCP joints thereby affecting hand capabilities extra [6].

Physicians ought to have a excessive index of suspicion when a affected person with presumed inflammatory arthritis isn’t responding to remedy or doesn’t have any indicators of energetic synovitis on full bodily examination. Hemochromatosis ought to be suspected when there’s a excessive iron profile and optimistic for HFE genotyping whereas destructive for RF and anti-CCP [7]. It’s, nonetheless, potential to seek out regular serum iron and ferritin stage with excessive transferrin saturation ranges in HH in line with Akgol et al. [7]. Feder et al. have decided that transferrin saturation stage is essentially the most delicate evaluation of iron overload within the physique and that the cut-off worth is over 45% [8].

Misdiagnosis as RA like on this case doubtlessly delayed the remedy and uncovered sufferers to steroid burden and unintended effects of disease-modifying brokers comparable to MTX [9]. The signs had been additionally not conscious of the disease-modifying remedy routine presumably resulting in the escalation of remedy to organic remedy.

Moreover, it’s important for sufferers with HH to have genetic testing of members of the family to foretell the probability of illness incidence in future generations. [3]. Misdiagnosis can, subsequently, not solely adversely have an effect on the affected person but in addition might doubtlessly trigger the rapid household to undergo sooner or later.

As HH has low penetrance, it’s much less prone to be cost-effective to do genetic screening in regular populations. Nevertheless, ferritin screening in sufferers with persistent progressive arthritis ought to be helpful as the majority price of ferritin testing is $5 per check [10].


It is crucial for physicians to know that HH is a crucial differential prognosis of RA. If misdiagnosed with RA as on this case, the signs wouldn’t have been relieved, and in addition there could be remedy burdens comparable to steroids and DMARDs together with MTX. Furthermore, it could have an effect on the long run era of the affected person as HH is a critical genetic dysfunction. It’s thus important to display hemochromatosis on a brand new prognosis of suspected RA sufferers with iron research. Extra research are really useful to focus on the significance of missed diagnoses and improve consciousness of main care and basic inside medication physicians.

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