Atypical cutaneous presentations revealing underlying multiple myeloma: A report of two cases

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Multiple myeloma (MM) is characterised by clonal expansion of plasma cells that secrete immunoglobulins or their fragments in the blood and/or urine. These disorders range from asymptomatic monoclonal gammopathy of undetermined significance to florid malignancies, including MM and plasma cell leukemia.¹ Cutaneous features are rare and usually seen in the later course of the disease. Herein, we present two cases initially presenting with cutaneous lesions.

A 62-year-old man presented with multiple painful lesions on acral areas with subsequent ulceration of one month duration. The lesions increased in size and number and had no tendency to heal. On examination, multiple purpuric macules with vesiculation, pustulation, bullae formation and central ulceration were present on bilateral legs, feet, hands, genitals and nose [Figures 1a-c]. The provisional diagnoses of vasculopathy, vasculitis and pustular pyoderma gangrenosum were considered. Investigations revealed anaemia (Haemoglobin-10.5 mg/dL), increased serum total protein (8.3 g/dL) and globulin (4.93 g/dL) levels with reversal of albumin-globulin ratio (AGR) (0.68:1). Cold serum samples and cryostat test were negative for cryoglobulins. Serum protein electrophoresis revealed a double M band in the β-2 and γ-globulin region. Histopathological examination of a purpuric macule showed features of vasculopathy with mid and deep dermal vessels filled with eosinophilic amorphous material and minimal surrounding inflammation [Figure 1d]. A diagnosis of MM was considered, which was confirmed by the presence of 70% plasma cells infiltrating the bone marrow. The patient was transferred to haematology. Chemotherapy with bortezomib and lenalidomide was started, and the patient is currently being followed up.

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Figure 1a:

Bilateral legs and feet showing multiple purpuric macules with vesiculation/bullae formation and a few lesions showing central necrosis and ulceration.

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Figure 1b:

Left leg showing multiple crusted ulcers with surrounding purpura (sutures are seen in situ at the biopsy site).

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Figure 1c:

Nose showing purpuric patch with central necrotic crust.

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Figure 1d:

Histopathology showing deep dermal vessels filled with eosinophilic amorphous material with minimal surrounding inflammation, consisting of lymphocytes and neutrophils (Haematoxylin and eosin,400×).

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Our second case is a 47-year-old man presented with redness and blisters on the lower legs for two weeks. These lesions subsequently developed bullae, some haemorrhagic, forming irregular erosions. On examination, multiple vesicles, bullae and erosions on a background of pedal oedema were present on bilateral legs, feet, and left knee [Figures 2a and b]. Haemorrhagic crusting and purulent discharge were also noted. The provisional diagnoses of pompholyx-like bullous pemphigoid and erythema multiforme were considered. A skin biopsy was done from the ulcer margin. Later, a few blisters developed retiform purpuric morphology, adding a diagnosis of vasculopathy. Laboratory investigations revealed severe anaemia (Haemoglobin-5 g/dL) with increased ferritin (298 ng/mL), lactate dehydrogenase (304 U/L), increased serum total protein (11.9 g/dL), and globulin (9.8 g/dL) levels with reversal of AGR (2:9). Cold serum samples and cryostat test were negative. Histopathological examination showed deep dermal vessel congestion with erythrocytes and eosinophilic amorphous hyaline material with minimal surrounding inflammatory infiltrate [Figures 3a and b]. The diagnosis of MM was confirmed by M band in the γ-globulin region on serum protein electrophoresis and bone marrow biopsy, revealing 80% plasma cells. The patient was started on chemotherapy and is under follow-up.

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Figure 2a:

Bilateral legs and feet showing purpura with overlying vesicles/bullae and ulceration on a background of pedal oedema. Haemorrhagic crusting and purulent discharge are seen on a few ulcers.

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Figure 2b:

Left knee showing dusky erythema and vesiculation.

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Figure 3a:

Histopathology showing deep dermal vessel congestion with red blood cells and eosinophilic amorphous hyaline material with minimal surrounding inflammatory infiltrate (Haematoxylin and eosin, 100×)

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Figure 3b:

Histopathology showing deep dermal vessel congestion with red blood cells and eosinophilic amorphous hyaline material with minimal surrounding inflammatory infiltrate (Haematoxylin and eosin, 400×)

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A recent Korean case series reported an incidence of 1.14% of cutaneous manifestations in patients with MM.² Cutaneous manifestations in MM can be direct or indirect and occur through one of three mechanisms: aggregation of misfolded monoclonal immunoglobulins or their fragments, deposition of malignant plasma cells or monoclonal proteins and antibody-mediated activity of the monoclonal protein. The vascular manifestations of MM include leukocytoclastic vasculitis (LCV), cryoglobulinaemic vasculitis, cutaneous vasculopathy and venous or arterial thromboembolism [Table 1].³ Clinically, these may present as purpura, haemorrhagic bullae, ulcers or livedo reticularis. LCV is mediated by immune complex deposition, which activates both the classical and alternative complement pathways.⁴ Cryoglobulinaemic vasculitis and vasculopathy occur due to the deposition of cryoglobulins and immunoglobulins that precipitate at temperatures below 37°C.^5-6 In our cases, the observed vasculopathic changes are likely attributable to hypercoagulability, a known complication in MM. This is proposed to result from the following mechanisms: alteration of fibrin structure by immunoglobulins, production of procoagulant autoantibodies, endothelial dysfunction induced by inflammatory cytokines and acquired resistance to activated protein C.⁷

The early diagnosis and treatment of MM are important as they impact prognosis. The presence of common clinical features, including fatigue, bone pain, fractures, renal failure and hypercalcaemia, often aids in early clinical suspicion. However, both of our cases were unusual in that the hallmark features were absent, and it was the initial cutaneous presentation that led to the diagnosis. Moreover, the skin lesions displayed diverse morphologies, mimicking features of vasculitis, vasculopathy, pyoderma gangrenosum, bullous pemphigoid and erythema multiforme. These findings underscore the importance of clinical vigilance and the need to recognise subtle laboratory pointers, such as a reversed AGR, which was observed in our cases.