Stones may grow on breasts and faces!

*It is only for medical professionals to read for reference.
Tophi is too crazy! Hyperuricemia is a common clinical disorder of purine metabolism.

According to the epidemiological data cited in the "Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China" released in 2020, the overall prevalence of hyperuricemia and gout in China is 13.
3% and 1.
1% respectively [1].

When urate crystals are deposited in soft tissues such as joints, subcutaneous, tendons and ligaments, they can cause chronic inflammation and fibrous tissue hyperplasia, and the resulting hard nodules are called tophi.

For patients who have not been treated after the first attack of acute gouty arthritis, the course of the disease usually exceeds 10 years to develop tophi, but 16% of patients can develop subcutaneous tophi within 10 years, and tophi may be the first symptom of gout [2].

There are three main areas in tophi: the central crystalline core with monosodium urate crystals as the core, the corona zone with densely distributed cells on the outside, and the fibrovascular area at the outermost layer.
(Fibrovascular zone)[2].

Figure 1 Cell pattern diagram of tophi [2] The volume of tophi can be as small as sesame, as large as an egg or even larger.
Its common parts include the first metatarsophalangeal joint, auricle, forearm extension side, finger joints, elbow joints, Olecranon and Achilles tendon.

However, there is no such thing as an unattainable place beyond your expectation of crazy tophi! The following author counts some cases, hoping to let everyone re-understand the tophi in a different place.

Tophi on the face.
Tophi rarely occurs on the face.

For patients with gouty arthritis with facial lesions, especially when these lesions are closely related to the symptoms of gouty arthritis, the possibility of tophi should be considered.

Morris WR et al.
reported a case of gouty arthritis in a 44-year-old man with gouty arthritis in a sub-journal of JAMA.
He saw a 4 mm subcutaneous mass on the lateral canthus of his right eye and it gradually increased for 1 year.

This is a hemispherical subcutaneous yellow mass, without pain and other inflammatory manifestations.

The examination of conjunctiva, cornea, anterior chamber, and pupil showed no abnormalities.

The histopathology after resection and biopsy was confirmed to be tophi [3].

Figure 2 Right eye lateral canthus tophi [3] Richards E et al.
also reported a case of a 55-year-old man with a 35-year history of gouty arthritis (tophi on his left elbow) in the BMJ sub-Journal.
The patient’s nasal dorsal area for 4 years Intermittent swelling and pain with nasal congestion and altered sense of smell often occur at the same time as arthralgia.

No intracavitary lesions were found during nasal endoscopy.

CT scan of the sinuses showed a subcutaneous mass on the nasal bridge with punctate calcification.

Biopsy confirmed tophi [4].

Figure 3 CT shows calcification of subcutaneous tophi in the dorsal area of ​​the nose and sinuses [4] periungual tophi finger/toenail is an atypical site for tophi.

Vela P et al.
wrote in the New England Journal of Medicine and reported a case of a 77-year-old man who found painless white lesions of the nail skin for 2 days [5].

Nail skin lesions may lead to impaired methyl quality, and patients also have nail changes.

The patient’s elbows showed tophi-like lesions.

One week ago, the patient had acute arthritis of the left wrist.
After the joint puncture, the synovial fluid examination showed the presence of urate crystals, so it was confirmed to be gout.
He was treated with prednisone and colchicine.

After the doctor collected the specimens from the nail skin, they observed them under ordinary light (Figure B), polarized light (Figure C) and compensated polarized light (Figure D), and found a large number of monosodium urate crystals.

After 4 months of treatment with allopurinol, the patient's perithyroid deposits disappeared and the tophi of the elbow became smaller.

Figure 4 Nail skin lesions (A) and the normal light (B), polarized light (C) and compensated polarized light (D) morphologies of monosodium urate crystals under the microscope [5] Breast tophus solitary breast gout nodules It may be the first and only manifestation of asymptomatic female gout patients with no previous medical history.

Sharifabad MA and others reported a case of a 38-year-old female who was physically fit [6].

During the first breast mammography screening, a nodule about 1 cm in size was found in the upper left quadrant of the left breast.
The patient did not have any breast discomfort or nipple discharge.

The breast examination showed no deformities, breast masses, and lymphadenopathy were not palpable.

Figure 5 The mammogram on the breast shows nodules in the upper left quadrant of the left breast; under a polarized light microscope, monosodium urate crystals with negative birefringence can be seen [6] Further breast ultrasound examination also showed that the patient has breast nodules.

Subsequent fine-needle aspiration biopsy revealed atypical epithelial cells and unshaped material.

Excision biopsy revealed benign cysts with chronic inflammatory changes, and needle-like crystals of negative birefringence can be seen under a polarized light microscope, which is consistent with the diagnosis of breast tophi.

Diffuse skin tophi may appear as atypical skin lesions such as pustules, ulcers, and panniculitis.
Diffuse tophi is not common.

Parlindungan F et al.
reported a 46-year-old man with recurrent gouty arthritis for 2 years.
The patient did not receive regular diagnosis and treatment [7].

In the past two years, diffuse yellow, tough subcutaneous nodules and plaques appeared on the skin of the patient's trunk and upper and lower limbs, some of which were accompanied by ulcers.

This time I visited the doctor due to acute polyarticular pain.

Figure 6 Diffuse tophi on the skin of the trunk and upper and lower limbs [7] Laboratory examination showed creatinine 203.
32 μmol/L and uric acid 11.
5 mg/dl.

Renal ultrasound showed nephrocalcinosis.

Subcutaneous nodule biopsy confirmed that it contained urate crystals.

The patient’s diagnosis was chronic gout with extensive skin lesions.

Due to the patient's renal impairment, the doctor recommended the use of methylprednisolone (8 mg tid for 5 days, then gradually reduced), colchicine (0.
5 mg qod), and allopurinol (100 mg qd).

The patient's pain was significantly relieved.

Valvular tophi When the echocardiogram of patients with hyperuricemia shows valvular hyperechoic disease, the differential diagnosis of valvular tophi should be considered.

Gout is associated with an increased risk of congestive heart failure and systolic dysfunction [8].

Rohani A et al.
reported a case of a 75-year-old man with multiple tophi on both hands, feet, elbows, knees and ankles and his condition worsened in the past 10 years [8].

Blood biochemistry showed that uric acid rose to 11.
4 mg/dl (2-7.
4 mg/dl), urea rose to 110 mg/dl (10-50 mg/dl), and creatinine rose to 1.
8 mg/dl (0.
5-1.
3 mg/dl) .

Liver function, serum electrolytes, and urine routine tests were normal, and rheumatoid factor was negative.

Transthoracic echocardiography showed a 1.
5×1×1 cm oval hyperechoic mass on the posterior leaflet of the mitral valve.
The valve opening area was not significantly reduced (3.
0 cm2), but there was mild mitral regurgitation and aortic valve Reflux.

Transesophageal echocardiography further confirmed the aforementioned examination results.
There was no obvious valve dysfunction, and it was considered to be valvular tophi.

Figure 7 Multiple tophis in the hand with joint deformities; transthoracic echocardiography shows an oval hyperechoic mass on the mitral valve (arrow) [8] The prevalence of spinal gout may be higher than imagined.
For spinal cord compression Patients with symptoms should consider the possibility of spinal gout.

Lumbar tophi (possibly ruptured) may also cause cauda equina syndrome [9-11].

Romero AB and others reported a case of an 82-year-old man with gout associated with tophi in the elbow and metatarsophalangeal joints for 40 years.
The patient had a new progressive spinal cord disease (hand numbness, paresthesia, lower limb dysfunction) in the past 3 months [9]. CT of the cervical spine showed severe arthritis changes and ankylosis of the middle cervical spine.
Calcification was seen in the mass after the dentate process.
The mass appeared to originate from the transverse ligament of the atlas with spinal cord compression and spinal stenosis was about 80%.

Figure 8 CT of the cervical spine: Sagittal image showing the mass of the transverse ligament of the atlas Note: Axial image showing the structure of the axis odontoid (A), lateral mass (B), and atlas nodule (C) [9] In addition, the currently reported atypical sites of tophi include tarsal canal, patellar tendon, second metacarpal bone, posterior talar triangle, genitals, bronchus, liver and other sites.

It can be seen that there are only unexpected, no crazy tophi far away! Therefore, for patients with a long-term history of hyperuricemia or gout, when there is a mass of unknown etiology, the possibility of tophi occurring in atypical parts should be considered.

It is worth noting that patients without a history of gout may also have atypical tophi as the first manifestation, and clinical attention should be paid to confirm the nature of the mass through imaging examination or biopsy in time.

Reference materials: [1] Chinese Medical Association Endocrinology Branch.
Guidelines for the diagnosis and treatment of hyperuricemia and gout in China (2019)[J].
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