Myoglobinuria: round up more than the usual suspects

Saban Elitok, Ute Kettritz, Jan Hinrich Bräsen and Ralph Kettritz

HELIOS-Klinikum-Berlin, Franz Volhard Clinic, Department of Radiology and Department of Pathology, Medical Faculty of the Charité, Humboldt University, Berlin, Germany. Email: kettritz{at}fvk-berlin.de

Case

A 72-year-old man was referred to the nephrology service because of myoglobinuria. The referring physicians were concerned that he might develop acute renal failure. Indeed, the myoglobin concentration in a sample of urine was 4757 µg/l, whereas his creatine kinase activity was 6287 U/l and his lactic acid dehydrogenase was 936 U/l. Anti-nuclear antibody titres were markedly elevated at a titre of 1:20 000 while anti-double-stranded DNA antibodies were not present. Serum creatinine concentration and cystatin C concentrations were not elevated and he denied having dark urine. Although the dipstick was slightly positive for blood, he had only several granular casts in his urine. A serum electrophoresis showed no monoclonal protein; however, immunofixation of serum and urine was positive for kappa light chains. The total amount excreted per 24 h was <0.5 g/day. The bone marrow showed a modest increase in plasma cells.

He reported that he was no longer able to perform the 50 pushups he had regularly managed until several weeks prior to admission. Furthermore, he now noted difficulty in climbing stairs. He also reported chronic pain in the shoulder girdle and thighs. His hand strength had also decreased. His physical examination revealed normal blood pressure and heart rate. Musculoskeletal examination showed weakness in the shoulder musculature, biceps, triceps, handgrip and quadriceps. His hands also showed nail atrophy and violaceous plaques on the dorsal aspects, as shown in Figure 1Go. Further questioning revealed a 4 kg weight loss. In addition, the patient had been operated upon 18 months earlier for a signet-cell gastric carcinoma. The tumour was reported to be superficial and a complete resection was possible. Lymph nodes were negative and several subsequent gastroscopies showed no sign of recurrence.



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Fig. 1.  Violaceous plaques (Gottron papules) were present on the dorsal aspect of both hands.

 

Questions

What is your diagnosis? What additional tests might help?

Answers to the quiz on the previous page

More diagnostic tests were performed to find a rationale for his muscular pain in the shoulder girdle and his thighs. An electromyogram was consistent with myopathy. A magnetic resonance image (MRI) of his shoulder musculature is shown in Figure 2Go. A muscle biopsy was consistent with myositis and is depicted in Figure 3Go. A dermatologist consultant agreed that the patient's violaceous rash was typical for dermatomyositis. Therapy with prednisone 50 mg/day was initiated and resulted in little improvement. We attempted to establish recurrence of his tumour. However, a repeat gastroscopy with multiple biopsies was negative and no metastases were found. Still to be tried are a course of immunoglobulins and azathioprine.



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Fig. 2.  T2-weighted fat suppressed MRI with striking enhancement demonstrating marked oedema within several isolated skeletal muscles.

 


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Fig. 3.  Histopathology of (A) skin lesion revealing unspecific perivascular predominantly lymphocytic inflammation and vacuolization of basal keratinocytes with formation of blebs (arrows); (B) muscle biopsy showing similar perivascular inflammatory infiltrates (arrow) and centrally located muscle nuclei (arrowheads) indicating regenerating fibre; (A and B) haematoxylin eosin stain, both original magnification x20.

 
Nephrologists must be aware of haeme pigment-induced tubular necrosis. Trauma, severe exertion, alcoholism, cocaine abuse, hypokalaemia, HMG Co-A reductase inhibitors, snakebite and viral infections should all be considered. Patients with rhabdomyolysis typically present with the triad of pigmented granular casts, brownish urine and a marked elevation in the plasma level of creatine kinase [1,2]. No features of the triad were present here. The degree of serum muscle enzyme elevation does not always predict the development of acute renal failure in rhabdomyolysis although there is a general correlation. A value >15 000 U/l would be expected. In one study, 58% of patients who developed acute renal failure had peak creatine kinase levels >16 000 U/l compared with only 11% in those who did not develop acute renal failure [1]. Myoglobin has a molecular weight of 17 000 Da and is therefore freely filtered and excreted, explaining the high myoglobin content of the patient's urine.

The patient's hand findings were typical [3]. The MRI scan was striking. Dermatomyositis is an inflammatory myopathy. Important is the association between dermatomyositis and cancer. Data reported by Hill et al. [4] found that 18–32% of patients with dermatomyositis have had, have, or will develop a cancer. The most likely cancers are those of the ovary, lung, pancreas, stomach, colon, rectum and non-Hodgkin lymphoma. We draw attention to the fact that multiple myeloma is a non-Hodgkin lymphoma in the broader sense and several cases of multiple myeloma with dermatomyositis have been described [5]. We could not establish the diagnosis of multiple myeloma in our patient, although the presence of kappa light chains in serum and urine is intriguing. Finally, the markedly elevated antinuclear antibody titre was a prominent feature in our patient, a finding that occasionally occurs in dermatomyositis [6]. Our patient draws attention to the fact that nephrologists must above all be good internists. You never know what might turn up next.

References

  1. Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med1988; 148:1553–1557[Abstract]
  2. Grossman RA, Hamilton RW, Morse BM, Penn AS, Goldberg M. Nontraumatic rhabdomyolysis and acute renal failure. N Engl J Med1974; 291:807–811[ISI][Medline]
  3. Herzinier T, Schorling S, Röcken J, Röcken M. A hoarse voice. Lancet2002; 359:1308.[CrossRef][ISI][Medline]
  4. Hill CL, Zhang Y, Sigurgeirsson B et al. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet2001; 357:96–100[CrossRef][ISI][Medline]
  5. Chakraverty R, Rabin N, Peggs K, Robinson S, Duncan JR, Yong K. Dermatomyositis and sarcoid-like reaction associated with multiple myeloma treated effectively by high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Bone Marrow Transplant2001; 27:1215–1217[CrossRef][ISI][Medline]
  6. Seligmann M, Cannat A, Hamard M. Studies on antinuclear antibodies. Ann N Y Acad Sci1965; 124:816–832[ISI][Medline]




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