A 29-year-old girl who took "herbal supplements" for half a year had rheumatism? | Wind list finalized

*It is only for medical professionals to read for reference.
Do you still dare to eat "herbal"? "Herbal medicine" or "tonic" as an emerging alternative mode of drug treatment has attracted much attention.

Some people have heard that certain "herbs" can strengthen the immune system, and they have been used as "tonics" for a long time.

However, the safety and efficacy of such drugs may need to be further explored.

Case introduction: A 29-year-old female who went to see a doctor in August 2015.
The main complaint was that her urine was green and foamy (see Figure 1), accompanied by lower limb edema.

The patient has no extrarenal manifestations such as arthritis, serositis, skin or blood system abnormalities.

He was in good health in the past, and there was no sign of infection before the onset.
The patient's physical examination in 2014 was normal.

 Figure 1 Patient's urine For nearly six months, the patient has been taking a herbal supplement called "Super kidney" (translated as "Super kidney"), which contains a variety of herbal ingredients.

Apart from this, no other drugs were taken.

Upon further questioning, the patient informed that the “super kidney” was brought from abroad and was not registered with the National Drug Administration, so the safety profile and details of it could not be obtained.

 Improve related inspections: Urine tests revealed proteinuria, 24h urine protein 10g, creatinine 47μmol/L, albumin 11g/L, and peripheral blood cell counts were normal.

Hepatitis B, hepatitis C and HIV were all negative, ANA was positive (titer 1:640), C3 and C4 levels were low, and anti-Smith, anti-RNP, anti-Jo and anti-SCL70 antibodies were all negative.

Both anti-SSA antibodies and anti-SSB antibodies were positive.

The erythrocyte sedimentation rate was 120 mm/h, and the C-reactive protein was normal.

 Kidney biopsy results suggest that according to the 2003 ISN/RPS lupus nephritis pathological classification, it is in line with IV-S (A/C) and V lupus nephritis, as well as secondary membranous proliferative glomerulonephritis.

Figure 2 Kidney pathological biopsy From the perspective of kidney biopsy, laboratory tests and clinical manifestations, the physician speculates that the cause of the patient's kidney damage is likely to be the lupus-like manifestations caused by the "super kidney" she took.

After stopping the drug, he was given prednisone 1 mg/kg, plus low-molecular-weight heparin.

After 6 weeks, the patient's edema was significantly reduced, and the urine returned to normal color.

The 24-hour urine protein was 3.
8g, the blood creatinine was maintained at 62μmol/L, the albumin level was 15g/L, and hydroxychloroquine and angiotensin-converting enzyme inhibitor were added.

 After 9 weeks of treatment, the patient still developed persistent proteinuria, with a blood creatinine of 66 μmol/L, a 24-hour urine protein of 5.
6 g, and albumin of 17 g/L.

After that, the patient started intravenous cyclophosphamide treatment, and the response was good without adverse reactions.
After the sixth injection, the patient was relieved.
The patient continued to take prednisone and gradually reduced the dose.

 Case summary The case in this article is derived from a case report abroad.

In this case, the patient’s previous physical examination did not find any abnormalities until after taking this herbal supplement, he developed nephrotic syndrome.
Further examination revealed low serum complement levels and positive antinuclear antibodies.
A kidney biopsy revealed lupus nephritis.

After stopping taking the drug, the kidney condition did not improve.
After intravenous injection of cyclophosphamide, the condition was relieved.

 Seeing this, you may have some questions: Since drug-induced lupus (DIL) is considered, why the patient's kidney condition has not improved after stopping this herbal supplement? It is speculated that the reasons may have the following explanations: First, this case may reflect the atypical manifestations of DIL, that is, the renal function has not improved after drug withdrawal; Second, it cannot be completely ruled out that the patient accidentally suffered from the drug or during drug withdrawal The possibility of systemic lupus erythematosus (SLE), after all, the patient responds to cyclophosphamide treatment.

Whether this is true DIL, or whether the herb has induced pre-existing lupus is still uncertain, and follow-up observation is needed.

Next, in conjunction with this case, let's understand the relevant knowledge of DIL~ DIL refers to the lupus-like syndrome caused by taking a certain drug.
At present, more than 80 drugs are known to induce DIL.

It has been reported at home and abroad that there are many kinds of herbs with nephrotoxicity.

The type of injury may be diverse, such as acute tubular necrosis, acute interstitial nephritis, chronic interstitial nephritis and electrolyte disturbances.

However, case reports of lupus-like syndrome and lupus kidney damage caused by herbal medicine are extremely rare.

 In 1945, it was reported that sulfadiazine induced DIL, and the reports about DIL increased day by day.
In 1953, Morrow et al.
reported that after hydralazine was used, there was a clinical manifestation similar to the late onset of SLE, which was confirmed by Dustan et al.
in 1954 ; In 1955, penicillin was found to cause lupus; in 1957, it was reported that anticonvulsants could cause DIL; although procainamide and hydralazine were used in clinical practice almost at the same time, it was not reported by Ladd until 1962 The first patient developed SLE-like clinical manifestations after 6 months of procainamide administration.

Since then, there have been some reports of adverse reactions to lupus-like syndrome caused by other drugs.

 Patients usually develop symptoms after taking the medication, and the symptoms may gradually get worse with the prolonged period of medication.

Most can manifest as fever, weight loss and fatigue, accompanied by musculoskeletal symptoms, the most common being joint pain.

There are very few cases of renal involvement, and only a few case reports describe the manifestations of lupus renal damage after penicillamine and propylthiouracil administration.

 Although the literature has more descriptions of DIL, there is still a lack of guidelines for diagnosis and treatment, and there is a lack of unified diagnostic criteria.

The diagnosis is mainly based on the time connection of symptom improvement after administration and discontinuation of the drug.

In most cases, the symptoms are similar to SLE, but the severity is much less severe.

In DIL patients, involvement of the kidneys and central nervous system is very rare.

Laboratory tests can detect the presence of autoantibodies, but the presence of antibodies is not a decisive condition for the diagnosis of DIL.

 There may be many ways to produce autoantibodies, including cross-reaction between anti-drug antibodies and nuclear antigens directly induced by drugs, and inhibiting immune tolerance to autoantigens.

DIL is related to genetic factors, including invalid alleles such as chronic acetylation, HLA-DR4 genotype, HLA-DR0310 genotype and complement C4.

In most cases of DIL, the symptoms of SLE disappear after the relevant drugs are stopped, and a very small number of patients have clinical symptoms that do not subside after stopping the drug, or have severe pericarditis and pericardial tamponade, pleurisy, and pleural effusion.

 Conclusion This case reminds us that herbal medicine has the possibility of inducing lupus nephritis.
In clinical work, attention should be paid to detailed drug taking history.

In addition, further research may be needed on the health effects of such drugs, and stricter supervision may be required in the future.

Regarding DIL, more clinical case reports and analysis are needed in the future, which will be more helpful for standardized diagnosis, treatment, and prevention of the disease.

 References: [1]Abdul Rashid AM, Abd Ghani F, Inche Mat LN, Lim CTS.
Herbal medication triggering lupus nephritis-a case report.
BMC Complement Med Ther.
2020 Jun 2;20(1):163.
[2] Zhang Daoyou, Xu Li.
Drug-induced lupus[J].
Clin Zhihui, 1999, 14(024):1127-1129.
[3]Lu Fuai, Wang Yongfu.
Research progress of drug-induced lupus[J].
Chinese Journal of Practical Internal Medicine, 2013 , 033(002):157-1