Presentation

A 30-year-old female community nurse presented at our outpatient rheumatology clinic with painful finger joints, intermittently flaring during a 10-year period. She reports sudden, painful 2-week-long arthritic episodes which she treated with over-the-counter NSAIDS. There is no family history of any rheumatic diseases, and the patient reports a smoking habit of 6 cigarettes daily, no use of alcohol nor drug. Lab values were normal (RF/ACPA/ANA negative, normal TSH, potassium 3.9 mM, serum Ca 2.27 mM, phosphate 1.2 mM, eGFR > 90, CRP 1 mg/dL, and ESR 8 m/hr). No signs for hyperparathyroidism, hyperthyroidism, or Gitelman syndrome were found. Physical examination revealed no abnormalities except bony thickening around proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints. Radiographic imaging showed non-erosive periarticular calcinosis at both hands: right DIP-2, PIP-2,4, and MCP-3,5 and left DIP-5, PIP-3,5, and MCP-1,2,4 (Fig. 1A), which do not fulfil the radiological definition of CPP [1]. The patient agreed on arthrocentesis. The puncture revealed some microscopical white particulate matter which was used for analysis with polarization microscopy (PLM) and Raman spectroscopy. PLM showed a dense amorphous structure (Fig. 1B). Raman spectroscopic analysis revealed that these structures consisted out of basic calcium phosphate crystals  (Fig. 1C, D) [2].

Fig. 1
figure 1

Raman spectroscopic analysis of basic calcium phosphate structures identified in joint punctate. A X-ray of left hand showing dense bone-like ectopic structures. B Polarized light microscopic image demonstrating a large, dense amorphous structure. C Raman spectrum measured within the identified structure. Peaks in the 430, 585 and 950 cm−1 are indicative of basic calcium phosphate crystals. D Hyperspectral Raman image of structure in B). Shown is the relative intensity of the 950 cm−1 phosphate peak

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Discussion

Depositions of pathologic crystals can be manifest in and around the human joints. Polarized light microscopy is commonly used to identify crystals, but BCP crystals are difficult to identify as they lack birefringence [3]. Here we demonstrated how Raman spectroscopy can be applied for easy identification in a clinical setting.

BCP is known to deposit in the shoulder, known as the Milwaukee shoulder syndrome [2], but, as we demonstrated, can also be deposited in smaller peripheral joints. Radiographically, BCP crystals and for example CPP chondrocalcinosis are indistinguishable and only with advanced analytical methods such as Raman spectroscopy patients can properly be diagnosed.