A RARE CASE OF MYOGLOBIN NEPHROPATHY CAUSED BY PARANEOPLASTIC DERMATOMYOSITIS SECONDARY TO SMOLDERING MULTIPLE MYELOMA

Dermatomyositis (DM) is an inflammatory myopathy that may form part of a paraneoplastic presentation secondary to various malignancies. An uncommon association is with plasma cell dyscrasias.

Myoglobin nephropathy is an uncommon complication of inflammatory myopathies which include polymyositis (PM) and dermatomyositis (DM). The mechanism of injury is rhabdomyolysis which causes muscle destruction leading to myoglobinuria which precipitates in kidney tubules causing acute tubular necrosis (ATN).1

This case describes such a presentation where the reason for referral was proteinuria. 

A 58-year-old mixed-race gentleman presented as an outpatient with the primary reason for referral being sub-nephrotic range proteinuria on a 24-hour urine specimen. On consultation and examination, he reported a 5-month history of a typical heliotrope rash; erythematous rash on his elbows and the V- sign forearms. Typical gottrons papules (Figure 1) on his metacarpophalangeal joints and periungal telangiectasia (Figure 2) on each nail bed. There was no peripheral oedema. There was no history of macroscopic haematuria or frothy urine. There was a 1-month history of bilateral proximal weakness of both arms with power of 3/5 on the oxford scale. These findings were suggestive of dermatomyositis.  

The only comorbidity was hypertension for which he was taking a combination tablet consisting of 10 mg amlodipine, 160 mg valsartan and 12.5 mg hydrochlorothiazide. There was no history of anti-inflammatory use or illicit dry use.

The patient was admitted to hospital for further work up. There was no significant albuminuria, and this pointed to another protein in the urine besides albumin. The creatine kinase was significantly raised and there was microscopic haematuria which suggested that the cause of the proteinuria may be myoglobinuria. (Table 1) Urine dipstick detects peroxidase activity of heme, and this is present both in red blood cells and myoglobin. A kidney biopsy was performed to elicit the cause of the proteinuria (Figure 3). The light microscopy showed features of acute tubular necrosis (ATN) with simplification of the tubular epithelium with loss of the brush border. The immunohistochemical myoglobin stain was positive (Figure 3E). Congo red stain was negative for amyloid. 

 Laboratory results are shown in table 1. The clinical, histological and biochemical evidence lead to a diagnosis of dermatomyositis (DM) complicated by myoglobin nephropathy.

Further tests were performed to exclude underlying malignancy in the presence of DM in a 58-year-old gentleman. The CT chest and abdomen, gastroscopy and colonoscopy did not show any malignancy.

Serum electrophoresis and serum free light chains were performed and showed IgA Kappa predominance. The subsequent bone marrow aspirate and biopsy (Figure 4 A-E) showed an increased number of plasma cells, estimated at 15-20% (Figures 3B and 3E). Majority of the plasma cells were positive for kappa light chain (Figure 3G).

The patient was diagnosed with IgA kappa smoldering multiple myeloma (SMM) because of a lack of CRAB (hypercalcaemia, renal failure, anaemia and bone lytic lesions) criteria. 

DM forms part of a group of diseases classified as Idiopathic Inflammatory Myopathies (IIM) and includes polymyositis (PM). DM is characterized by the presence of characteristic cutaneous lesions (heliotrope rash, gottrons papules, periungal telangiectasia, shawl sign and V-sign) with or without proximal muscle weakness.  DM is paraneoplastic in up to 25% of cases.2 The risk of malignancy is similar in myopathic and amyopathic cases.3 There is no association between myositis related antibodies and paraneoplastic DM but there is an association between anti- transcriptional intermediary factor 1 gamma (TIF-1ɤ) , anti-nuclear matrix protein 2 (NXP-2) and anti- small ubiquitin-like modifier activating enzyme (SAE) antibodies. 2,3

The most associated malignancies are solid organ tumours, most frequently, breast, lung, ovarian and urothelial cancers. 2,3 Haematological malignancies are less common with only a handful of case reports in the literature. The more commonly associated haematological malignancies are lymphomas.4 From a large retrospective cohort involving 4641 patients with multiple myeloma or monoclonal gammopathy of unknown significance (MGUS), there was a 2.29 times relative risk of developing plasma cell dyscrasia in patients who presented with IIM.5

Cases of DM associated with multiple myeloma are rare with only a few documented case reports. The timeline of these cases is also var,iable with the diagnosis of  MM either preceding or following the diagnosis of DM. 6,7,8makes up 1.8% of all malignancies; the median age at diagnosis is approximately 65 years and it is almost two times more common in the black population.5

This case is the first case in literature documenting paraneoplastic DM as the form of presentation of SMM and it allowed for early detection and treatment to prevent organ damage.

 Inflammatory myopathies are associated with malignancies, but DM is significantly more than PM. In a cohort study the prevalence of malignancies was 32 % in patients with DM and 15% in patients with PM. 6

Chronic immune stimulation is considered the underlying mechanism which leads to T-cell and B-cell activation leading to the development of hematological malignancies like MM.5 Crossover immunity between myofibroblasts and tumour cells may reflect the simultaneous presentation of the two diseases.6

In this case the presentation of DM occurred concurrently at the time of diagnosis of smoldering MM. What makes this case interesting is the lack of biochemical or radiology features to suggest plasma cell dyscrasia, and had it not been because of the presentation with DM, the diagnosis of SMM may have been missed. It also emphasizes that although haematological malignancies are less commonly associated with paraneoplastic DM, it should form part of routine screening together with other investigations.

The revised international working group diagnostic criteria for multiple myeloma facilitates the early diagnosis of plasma cell disorders to allow for early treatment to avoid progression to end organ damage. 9 This case serves as a clear example of its utility in early diagnosis.

This patient was referred to a haem-oncologist and received 6 cycles of bortezomib/leflunamide and dexamethasone. His most recent blood results are shown in table 1.

A key point is that the reason for the referral was proteinuria, and this serves as a reminder of the core principles of history taking and clinical examination. This prompted further investigation into the type of protein in the urine. This case was referred to a nephrologist and highlights how urine analysis can be the harbinger of diagnosis of a systemic illness and must be done routinely in the form of a simple bedside urine dipstick test and not underestimated

References:

1.      Gomes RR. A Case of Dermatomyositis Presenting with Fulminant Rhabdomyolysis without Myoglobinuric Acute Kidney Injury—A Rare Clinical Manifestation. Arch Rheum Arthritis Res. 2020;1(3):ARAR.MS.ID.000512. doi:10.33552/ARAR.2020.01.000512.

2.     Requena C, Alfaro A, Traves V, Nagore E, Sanmartín O, Guillén C, et al. Paraneoplastic Dermatomyositis: A Study of 12 Cases. Actas Dermosifiliogr. 2014;105(7):675-682. doi:10.1016/j.ad.2013.11.007.

3.     Requena C, Sánchez-Romero E, Nagore E, Sanmartín O. Paraneoplastic Dermatomyositis: A 25-Patient Series from a Cancer Center. J Invest Dermatol. 2025;116(4):T444-T448.

4.     Marie I, Guillevin L, Ménard JF, Cherin P, Hachulla E, Mouthon L, et al. Hematological Malignancy Associated with Polymyositis and Dermatomyositis. Autoimmun Rev. 2012;11(9):615-620. doi:10.1016/j.autrev.2011.10.024.

5.     Shimanovsky A, Alvarez Argote J, Murali S, Dasanu CA. Autoimmune Manifestations in Patients with Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance. BBA Clin. 2016;6:12-18. doi:10.1016/j.bbacli.2016.05.004.

6.     Islam MS, Kotoucek P. Multiple Myeloma Associated with Dermatomyositis: A Short Report and Mini-Review. Int J Blood Res Disord. 2018;5:029. doi:10.23937/2469-5696/1410029.

7.     Muñoz J, Hanbali A. A Young Patient with Multiple Myeloma. Blood. 2012;119(13):2979. doi:10.1182/blood-2011-06-362905.

8.     Faria D, Silva J, Neves J, Rodrigues J, Afonso C, Peixoto D. Systemic Sclerosis and Myositis as a Paraneoplastic Syndrome Secondary to Multiple Myeloma. Acta Reumatol Port. 2018;43(2):316-317.

9.     Rajkumar SV. Multiple Myeloma: 2024 Update on Diagnosis, Risk-Stratification, and Management. Am J Hematol. 2024;99(9):1802-1824. doi:10.1002/ajh.27422.