How difficult is it to diagnose rheumatism?

*Only for medical professionals to read for reference to diagnose rheumatism, will you? In line with the original intention of "spreading the strongest rheumatism and creating a new academic fashion", on the occasion of leaving the old and welcoming the new, the "medical world" media teamed up with nearly 20 well-known experts in the field of rheumatism from the four top rheumatology departments in China, covering 8 rheumatism In the field of hot diseases, we will start the "Rheumatism and the Waves-2020 Annual Rheumatism Inventory".

In this issue, Professor Chen Sheng from Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine shared with us "Analysis of Difficult Cases of Rheumatism.
" It will let them escape the doctor's eyes.

In this regard, we have counted and analyzed the difficult cases of rheumatism recently published by Renji Hospital on the "Medical Circle Rheumatology and Kidney Disease Channel", so that these "cunning" intractable diseases should not be allowed to "escape"! What are the specific rheumatism incurable diseases for reference? Let's take an inventory! 01 Lupus and IgG4-RD can't distinguish between swollen lymph nodes, kidney involvement, positive multiple autoantibodies, and reduced complement.
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The first impression is systemic lupus erythematosus (hereinafter referred to as "lupus")? If you think so too, you may fall into a "trap".

 Case characteristics: The patient’s kidneys were large in appearance, right kidney hamartoma, suggesting occult renal insufficiency; elevated IgG4 and hypocomplementemia; multiple lymphadenopathy; bilateral inguinal masses without obvious cause, progressive increase Da et al; (For details, please click "The increase in blood creatinine, the inguinal lymph nodes are getting bigger and bigger, and it turned out to be.
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") Professor Chen Sheng pointed out that if the diagnosis is lupus or chronic granulomatous inflammation, the disease is There are the following doubts: a history of diabetes for more than 5 years; urine routine, urine total protein-creatinine ratio is normal; lymph node biopsy pathology is granulomatous inflammation; then, what is this disease? The results of the consultation in the Department of Pathology of Shanghai Pulmonary Hospital showed that: lymphoid tissue hyperplasia, small focal epithelial cell hyperplasia in lymph nodes, no acid-fast bacilli and fungi were found, and tuberculosis infection was not considered.Figure 1.
Pathological results of lymph nodes.
Renal biopsy showed severe tubulointerstitial lesions, a large number of lymphoplasmacytic infiltration with interstitial fibrosis, suggesting IgG4-related nephropathy.

 Figure 2.
Renal biopsy results Taken together, the patient's kidneys are too large in appearance, which is different from chronic kidney disease with reduced renal manifestations, and the disease is different from the typical manifestations of lupus nephritis.

In addition, the pathological results of lymph node biopsy specimens and kidney biopsy all point to lgG4-related diseases (IgG4-RD).

 It can be seen that the diagnosis of systemic diseases is often not easy.
In addition, some of the manifestations of IgG4-RD overlap with diseases such as lupus.
It is even more necessary for clinicians to analyze carefully and break the cocoon! 02 "Arthralgia" that causes deformity of hands and blindness occurs in infants and young children.
The clinical manifestations are rash, arthritis, and uveitis.
Repeated treatments have failed.
Behind this layer of fog, what disease is at work? Case characteristics: a transient whole body red rash in infancy; 4-5 years old, multiple joint deformities of hands, no obvious pain and swelling, accompanied by loss of binocular vision; multiple joint deformities of hands progressively aggravated, limited mobility, and only light loss of vision Feeling; at the age of 27, due to upper respiratory tract infection, fever, swelling and pain in multiple joints of both knees, etc.

(For details, please click "4-year-old hand joint deformity, and then blindness, I still go the old road of mother.
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") Let's take a look at the joint performance of the patient together: Figure 3.
The patient's hands After seeing the characteristics of patients with polyarticular deformities, Professor Chen Sheng realized that this kind of "arthralgia" is not simple! Questioning the patient’s family medical history revealed that both his mother and uncle had joint deformities, uveitis, and are currently blind.

 From this point of view, is there a possibility of genetic disease? After whole-exome sequencing + single-gene site verification of parents’ samples, the results showed that the patient’s NOD2 gene (chr16: 50744822) had a mutation in base 1001 of guanine to adenine (c.
1001G>A) on chromosome 16.
), and the mutation comes from its mother! Figure 4.
Genetic sequencing results of patients and their parents.
What genetic disease is this? Professor Chen Sheng pointed out that the disease is a single-gene autoinflammatory disease called Blau syndrome.
The typical affected parts are joints, eyes and skin, and it is manifested as arthritis, dermatitis, and uveitis.  This case reminds us that if the patient has repeated episodes of inflammation that cannot be explained by other reasons, we should suspect whether it is an autoinflammatory disease.

Through early detection and early treatment, the poor prognosis of patients may be avoided! 03 "Repeated leg soreness and weakness" is not a trivial disease! Repeated weakness in the legs, check it all over, the disease is not getting better, is it polymyositis? If not, what is going wrong? Disease characteristics: the patient is a middle-aged male, onset at the age of 30; symmetric proximal muscle weakness, increased muscle enzymes, abnormal electromyogram, CK up to nearly 20,000 U/L; muscle MR indicates myositis changes; muscle biopsy shows no inflammation Cell infiltration (for details, please click "Repeated leg weakness for 7 years, but repeated treatments have failed.
What is the strange disease?").

 Professor Chen Sheng pointed out that although the patient was diagnosed with polymyositis in the early stage, it conflicted with the following points: hormones, immunosuppressants, and gamma globulin seemed to be effective quickly after treatment, and sometimes the effect was not good; myositis antibody spectrum was negative; The course of the disease is long, but there is no lung involvement; there is a history of hyperthyroidism.

 Isn't it polymyositis? It seems that we are going to disrupt the original plan and re-analyze it! The re-reading of the pathology of the muscle biopsy showed that there were proliferation of collagen fibers in the dermis (skin of the right thigh), uneven thickness of striated muscle fibers, partial degeneration and atrophy, and a small amount of inflammatory cells in the interstitium.

 Figure 5.
Pathological results of muscle biopsy and then use myopathy-related gene panel sequencing to check whether it is metabolic myopathy: Figure 6.
Whole-exome sequencing results found that there are indeed two mutations in the patient’s ETFDH gene, and other auxiliary results suggest The patient is glutaric acidemia type II! It can be seen that the disease is really hidden, which also reminds rheumatologists that genetic examination is extremely important for a clear diagnosis.

 04 Young male "strange disease" started at the age of 10, intermittent fever, conjunctival congestion, urticaria, headache, joint pain.
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First, blurred vision, and then hearing loss.
Let's take a look at this "strange disease".

 Case characteristics: young male, childhood onset; multiple system involvement, sometimes accompanied by conjunctival congestion, sometimes accompanied by wind mass-like rash on the legs, etc.
; cold induced; high ESR and CRP. (For details, please click "I started "being ridden with strange diseases" when I was 10 years old.
When I was 22 years old, I was almost "blind"! The real culprit was.
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") The nipple border is unclear, pale, and blood vessels around the optic disc are occluded.

 Figure 7.
Fundus examination results Professor Chen Sheng noticed that the patient had repeated attacks for up to 12 years—relief of periodic fever accompanied by rash and arthritis.
Physical examination also found special signs such as clubbing and hyperkeratosis.
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  Figure 8.
Dry and desquamation of the skin on the soles of the feet.
Finally, the gene sequencing results showed that it was an autoinflammatory disease, Cryopyrin-associated cycle syndrome (CAPS).

 This case reminds us that doctors need to collect a detailed medical history and physical examination during the consultation process, especially for difficult cases, not to ignore every element and detail of the disease.

 05The "lupus" that cannot be corrected for anemia is caused by coughing and wheezing.
Why does anemia still appear during the treatment? Is it a misdiagnosis? Take a look! Disease characteristics: The patient developed a cough after being cold, with paroxysmal single cough, no sputum and hemoptysis, and improved after self-administration of cough medicine; pale skin and pale conjunctiva; during the course of the disease, the patient did not have repeated fever, rash, or oral cavity Ulcers, joint swelling and pain.

(For details, please click "I was accidentally diagnosed with "lupus", why can't the anemia be corrected?") During the treatment, the patient developed severe anemia.

Usually, patients with SLE combined with diffuse pulmonary hemorrhage are manifested as acute massive hemorrhage, so doctors suspect that it is anemia caused by lung infection, lupus pneumonia, and cardiac insufficiency.

   Figure 9.
Pulmonary HRCT findings.
However, after careful examination, the peak circuit turned around.
Professor Chen Sheng pointed out, is it SLE with diffuse pulmonary hemorrhage? as predicted! Bronchoscopy showed that hemosiderin-containing macrophages.

The patient has no clear manifestations of infection, pulmonary renal syndrome, heart failure, etc.
, and the antiphospholipid antibody is negative, which is indeed diffuse alveolar hemorrhage caused by SLE.  Figure 10.
Looking back on the results of the bronchoscopy, this case reminds us that in addition to acute massive bleeding in SLE patients with diffuse pulmonary hemorrhage, it can also be manifested as subacute chronic blood loss without obvious symptoms of hemoptysis.
This requires our focus.

 06Complications of "deadly" severe lupus! Case features: scattered rashes on cheeks and upper limbs, multiple joint swelling and pain in both hands, and positive tenderness in both lower limbs; heart rate reached 126bpm; oral ulcers, diarrhea and other abnormalities in the past two weeks (for details, please click "Severe Lupus + Continuous Fever" Because of this complication, "life hangs by a thread"!").

 The patient was quickly diagnosed as "not only suffering from rheumatoid arthritis, but also other autoimmune diseases.
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After confirming the diagnosis of SLE, the comprehensive diagnosis found that the situation was much more serious than expected! The patient's skin, blood, lungs, and gastrointestinal tract are affected, fever, and obvious skeletal muscle inflammation.

  Figure 11.
Plain MR scan of the patient's thigh, T2 fat suppression sequence.
However, the patient's heart rate also gradually decreased, further suggesting that his heart damage was far more severe than it initially appeared.

  Figure 12.
Myocardial MR results of the patient.
Although severe lupus has led the patient into the abyss, the complications of severe lupus deserve more attention from rheumatologists.

It can be seen that timely detection of myocardial inflammation and ischemic manifestations and assessment of cardiac function in the early stage can regain vitality for patients whose lives are hanging by a thread! 07 Summary At the end, let’s summarize.
Don’t panic about incurable rheumatic diseases.
Professor Chen Sheng pointed out that the following four main points should be kept in mind: diagnosis of the cause is a prerequisite, and rare diseases should be paid attention to; details and pathology should be paid attention to.
Detection methods, such as genes, imaging, next-generation sequencing, etc.
; professional knowledge should be learned through multiple channels and online.

 Expert profile Professor Chen Sheng, chief physician, master's tutor, doctor of rheumatology, postdoctoral fellow at the National Institutes of Health, the current deputy director of the Department of Rheumatology and Immunology, Renji Hospital, Shanghai Jiaotong University, member of the Rheumatology Branch of the Chinese Medical Association, member of the Chinese Medical Association Member of the Youth Committee of the Shanghai Rheumatology Association Member of the Rheumatology Group of the Chinese Medical Association Psychological Association Member of the Shanghai Pudong Rheumatology Association