Multiple myeloma-associated systemic amyloidosis | CCID

case report

An 81-year-old woman first presented to a dermatologist with petechiae, ecchymosis, and sometimes non-rupturable hemorrhagic blisters all over her body for 6 years without pain or itching. At about the same time, the patient discovered nail abnormalities, erythema, swelling of the palms, papules on the buttocks, and gradual flaccidity of the skin.

On physical examination, multiple petechiae, generalized Nissl-negative ecchymosis, abnormal skin wrinkling and laxity, symmetrical periorbital edema with purpura, and multiple fleshy areas of the face and anterior neck area. or brown waxy smooth papules (Figures 1-4), hard warts and papules on the left buttock (Figure 5), multiple nail dystrophy, erythematous swelling of the palms and toes.

Figure 1 There was symmetrical periorbital edema with purpura, and multiple cutaneous or brown waxy smooth papules on the patient’s face.

Figure 2 Purpura, petechiae, cutaneous ecchymosis, and nail dystrophy.

Figure 3 Erythematous swelling of the palms and toes.

Figure 4 The patient’s right groin showed ecchymosis with no apparent cause.

Figure 5 There was a hard wart-like plaque on the left buttock at 3 o’clock. Bleeding may occur after crushing.

Blood tests showed serum IgG 3.73 g/L (8.60–17.40 g/L), IgA 34.40 g/L (1.00–4.20 g/L), IgM 0.08 g/L (0.50–2.80 g/L), kappa light chain 3.45 was shown. g/L (6.29–13.50 g/L), lambda light chain 22.90 g/L (3.13–7.23 g/L), κ/λ 0.15 (1.53–3.29), clotting factor X 48.70% (77–131%).

Protein electrophoresis and immunofixation electrophoresis showed albumin 48.2% (54.0–65.7%), β2-globulin 32.3% (8.2–13.8%), γ-globulin 1.9% (10.6–23.5%), monoclonal IgA-α and monoclonal λ light chain was shown. It was M protein positive and IgA-λ type. Serum-free light chain was κ 6.2 mg/L (3.30–19.40 mg/L), λ 307.5 mg/L (5.71–26.3 mg/L), Fκ/Fλ 0.020 (0.26–1.65), and dFLC 301.3 mg/L showed. /L. Urinalysis showed protein assay 0.32 g/L, albumin 98.3%, monoclonal IgA-α positive, monoclonal λ, λ-type Bence–Jones protein, λ light chain 7.44 mg/dl (0.00–5.00 mg/dl), and 24-hour total urine volume were shown. Quantification of lambda light chain 130 mg.

Radiographic examination showed no abnormalities in the bilateral femur and humerus. A CT scan showed no obvious puncture-like bone destruction in the skull, no obvious bone destruction in the entire spine, ribs, sternum, or pelvic bones, but no degeneration in the neck and lumbar region. did not.

A bone marrow biopsy showed hypercellularity with plasma cell hyperplasia consistent with multiple myeloma.

Histopathological features of the abdominal skin showed the presence of eosinophilic, amorphous fissured material in the Congo red-staining positive dermis (Figure 6 and 7). Electron microscopy revealed that sheets of fine fibers with a diameter of 10 nm were randomly distributed in the dermis (Figure 8). Features were consistent with amyloidosis.

Figure 6 Histological features.

Figure 7 Congo red staining (+).

Figure 8 (a and B.) Electron microscopic observation revealed that fine fibers with a diameter of about 10 nm were randomly distributed in the dermis corresponding to amyloidosis.

The patient was diagnosed with multiple myeloma and multiple myeloma-associated systemic amyloidosis. No significant improvement in skin lesions was observed after treatment with the BD regimen (bortezomib regimen in combination with dexamethasone). The patient refused further treatment for financial reasons.

discussion

Immunoglobulin light chain (AL) amyloidosis (historically known as primary amyloidosis) is a rare disease and the exact incidence is still unknown. In the United States, the incidence appears to be stable at about 9-14 cases per million person-years.1–3 Elderly people are susceptible to AL amyloidosis. As with other plasma cell disorders, the age-specific incidence increases with each decade after age 40.¹ AL amyloidosis, in which fibrils are composed of fragments of monoclonal light chains. Affected patients may suffer from amyloidosis alone or with other plasma cell disorders (multiple myeloma, Waldenstrom’s macroglobulinemia). This part of AL amyloidosis is associated with multiple myeloma, in which the deposited light chains originate from bone marrow plasma cells and cause deposition and dysfunction in a wide range of organs.^4–6 Complex interactions exist between immunoglobulin-derived proteins, including light and heavy chains, and elastic tissue components, leading to various types of impairment of the latter.⁷ Therefore, AL amyloidosis can present with various clinical manifestations in dermatology, such as purpura, waxy thickening, ecchymosis and skin laxity.^7,8

Amyloid purpura is suspected to be associated with decreased clotting factor X, but this relationship has not been established. It has been observed that low levels of factor X activity were observed in approximately 1 in 4 samples in 36 patients.⁹ Since AL amyloidosis is a clonal plasma cell disease, it is treated with chemotherapy to eradicate the underlying clone. AL amyloidosis should be distinguished from other forms of amyloidosis (AA amyloidosis, ATTRmt amyloidosis, ATTRwt amyloidosis, etc.). Because the latter are non-neoplastic and do not benefit from chemotherapy. Compared to normal conditions, MM cells can have low or high levels of microRNAs (miRs) that are used as tumor suppressors or oncogenes. Due to the low expression of tumor suppressor miRs in cancer, there may be therapeutic benefit in restoring normal levels through miRs replacement strategies.^Ten

Conclusion

Our patient simultaneously presented with at least five different forms of skin lesions: purpura, flesh-colored or brown waxy smooth papules, warty macules, hemorrhagic bullae, and nail dystrophy. Congo red staining was used to confirm the presence of amyloid fibrils. Electron microscopic observation revealed that fine fibers with a diameter of about 10 nm were randomly distributed in the dermis, consistent with amyloid fibrils. The final diagnosis in this patient was multiple myeloma-associated systemic amyloidosis, as multiple myeloma was diagnosed by bone marrow biopsy according to the latest diagnostic criteria for multiple myeloma by the International Myeloma Working Group.

We report a case of multiple myeloma-associated systemic amyloidosis. In this case, the simultaneous appearance of multiple skin lesions at different sites in one patient is clinically rare. The morphology of skin lesions is diverse, making it difficult to identify the same skin disease. With regard to cutaneous manifestations, the morphology of the rash depends on the site of amyloid deposition, so when deposited in small blood vessels in the skin, skin lesions appear as petechiae, ecchymosis, and purpura. When it is deposited on the superficial layer of the dermis, waxy papules appear. Early cutaneous manifestations included multiple cutaneous manifestations in addition to the typical signs of amyloidosis. Petechiae and ecchymosis were the patient’s first symptoms.

ethics statement

Written informed consent for publication of clinical details and clinical images was obtained from patients. No institutional approval was required. This case report was prepared according to the CARE guidelines.¹¹

Disclosure

The authors report no conflicts of interest in this work.

References

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