Leukemia Research 24 (2000) 91–93

Case report

Relapsing polychondritis, smouldering non-secretory myeloma andearly myelodysplastic syndrome in the same patient: three difficult

diagnoses produce a life threatening illness

Rachel Hall *, Neil Hopkinson, Terry HamblinDepartments of Rheumatology and Haematology, Royal Bournemouth Hospital, Castle Lane East, Bournemouth BH7 7DW, UK

Received 1 April 1999; accepted 5 August 1999

Abstract

Multiple myeloma, relapsing polychondritis and myelodysplastic syndrome are all serious diseases in which making a cleardiagnosis can be difficult. This case of a 72-year-old man found after extensive investigation to have all three of the above,demonstrates how difficult diagnosis and treatment can be, producing in this case a life threatening clinical syndrome. We alsopostulate that the association of these three diseases may be an immune-derived complication of myelodysplastic syndrome.© 1999 Elsevier Science Ltd. All rights reserved.

Keywords: Myeloma; Immunoglobulins; Polychondritis

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1. Introduction

Both multiple myeloma (MM) and relapsing poly-chondritis have been previously reported in associationwith the myelodysplastic syndromes (MDS). We reporthere the first instance of all three occurring together.

2. Case report

The patient, a 72-year-old Caucasian male, presentedin September 1993 with a 15-month history of pruriticerythematous rash occurring sporadically over all fourlimbs. He had a swollen oedematous right arm. Therash consisted of raised red lesions 2–5 cm in diameter,some of them being target like. It was variously de-scribed by a dermatologist as ‘vasculitic’ and ‘erythemamultiforme-like’.

FBC showed Hb 95 g/l, MCV 96 fl, WBC 3.0×109/l(neutrophils 2.2; lymphocytes 0.5) and platelets 152×109/l. ESR was 124 mm in 1 h. Urea, electrolytes and

liver function tests, serum calcium and uric acid wereall normal. Serum immunoglobulins were slightly re-duced with IgG 5.5 g/l, IgA 0.9 g/l and IgM 0.8 g/l.There was no monoclonal band or Bence Jones protein-uria. Bone marrow aspirate showed 15% atypicalplasma cells which stained for IgGl. There were minordegrees of dyserythropoiesis including small numbers ofring sideroblasts, myeloid hyperplasia with some hypo-granular polymorphs, but normal megakaryocytes. Cy-togenetic studies were normal in the majority of cells,but one cell showed monosomy 7. Skeletal surveyshowed no bony lesions.

Right arm venogram showed a brachial and cephalicvein thrombosis. Cryoglobulins, autoimmune profile,ANCA and lupus anticoagulant screens were allnegative.

The patient was therefore diagnosed as having earlyMDS and early non-secretory myeloma, but no causewas identified for his skin lesions or venous thrombosis.He was anticoagulated with heparin and then warfarin.

In October 1993 he developed facial swelling withtenderness across the bridge of his nose. His Hb hadfallen to 86 g/l. The original rash was not evident but* Corresponding author.

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PII: S 0 1 4 5 -2126 (99 )00151 -4

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he had recurrent episodes of limb cellulitis requiringintravenous antibiotics. A CT scan to exclude an under-lying malignancy was normal. In December 1993 hedeveloped proptosis of the left eye with periorbitaloedema and cellulitis and was diagnosed as havingepiscleritis. In January 1994 he developed pain andredness in his left pinna. This was unresponsive toantibiotics but when prednisolone was begun a dra-matic response was seen in the ear swelling, rash andfatigue.

Between January and June 1994 he was treated withvariable doses of prednisolone and azathioprine. Hisskin lesions fluctuated in severity and he experienced afurther axillary vein thrombosis in his left arm duringthis time. In June 1994 because of an increasing trans-fusion requirement a further bone marrow aspirate wasperformed and revealed 24% plasma cells and moreobvious myelodysplastic features. He was treated withintravenous methylprednisolone and cyclophos-phamide. Despite initial improvement, the rash deterio-rated and was accompanied by multiple episodes ofsevere cellulitis. A skin biopsy was non-diagnosticshowing chronic inflammatory changes only. In August1994 the deteriorating skin condition was treated withdaily oral cyclophosphamide 100 mg and prednisolone20 mg but with little effect.

In November 1994 a rheumatological opinion wassought and a diagnosis of relapsing polychondritis wassuggested on the basis of diffuse scleritis, arthritis,painful red vasculitic skin nodules, inflammation ofpinna and nasal cartilages, recurrent thrombophlebitisand marked acute phase response. He was treated withpulsed intravenous cyclophosphamide and methylpred-nisolone over the next year but experienced recurrentepisodes of inflammatory rash and swelling and multi-ple episodes of sepsis due to his state of chronic im-munosuppression. He was treated with a variety ofimmunosuppressive drugs including methotrexate andcyclosporin and several antibiotics.

In November 1995 a bone marrow aspirate andbiopsy showed his myeloma to be stable but the MDShad progressed and was showing prominent ALIPs(abnormal localisation of immature precursors). ByJune 1996 there was obvious trilineage myelodysplasiawith 9% blasts in the marrow. Chromosomes remainednormal.

His disease ran a stormy course with multipleepisodes of inflammatory disease and sepsis, his anti-inflammatory therapy being interrupted by frequentinfections. His MDS progressed with increasing throm-bocytopenia and the need for regular red cell transfu-sions. The MM was not progressive and caused notrouble apart from contributing to the immunosuppres-sion. In January 1997, for the first time an IgGlparaprotein was detected in the serum. In February1997 the patient suffered an osteoporotic collapse of

D12. There were no other features of myelomatousbone disease, and the collapse was attributed to longterm treatment with corticiosteroids. The patient diedfrom bronchopneumonia in April 1997.

3. Discussion

Bergsagel [1] put the risk of acute leukaemia occur-ring in patients with MM at 230 times normal. Al-though some of this increased risk is related totreatment with alkylating agents, it is now well estab-lished that both acute leukaemia and MDS occur inMM patients not exposed to treatment [2,3]. It is likelythat plasma cell neoplasms are merely part of thedisorder of immune regulation that occurs in MDS withboth autoantibodies and monoclonal immunoglobulinsbeing unexpectedly common [4].

The diagnosis of MM in this patient was difficult toestablish. There were no bony lesions apart from a latevertebral collapse that was probably related to treat-ment with steroids. There was no paraprotein until latein the disease. The suppression of normal immunoglob-ulins was minimal and there was no Bence Jonesproteinuria. Diagnosis depended on the presence of15% monotypic abnormal plasma cells in the marrow,more than would be expected in MGUS. Stage Imyeloma or smouldering myeloma would be an appro-priate appellation.

Relapsing polychondritis is a rare chronic inflamma-tory disease. It is one of the systemic vaculitides and ischaracterised by episodes of inflammation of cartilagi-nous tissues, especially those of the nose, ear, joints andtracheobronchial tree. Since there are no specific tests;the diagnosis, which is difficult, must be made onclinical grounds. Systemic symptoms including fatigue,weight loss, fever and anaemia are commonly accompa-nied by a vasculitic rash and inflammation of proteo-glycan-rich structures such as the eye, heart, bloodvessels and inner ear [5].

The cause of relapsing polychondritis is unknown.There is an association with HLA-DR4 [6] and evi-dence of an immune response against type II collagen[7]. It is may be part of a range of features displayed bya number of different connective tissue diseases. Treat-ment is usually by immunosuppressive drugs, but thedisease is progressive and life threatening, and as in thiscase, treatment options are often limited by side effects.

The association with MDS has been described onseveral occasions [8–17] and it has been suggested thatup to a quarter of cases of relapsing polychondritis maybe associated with MDS, although, conversely, thesecomprise less than 1% of MDS cases [17]. We havepreviously postulated that immune complications ofMDS might be caused by disordered monocyte func-tion. We suggest that MDS monocyte-derived dendritic

R. Hall et al. / Leukemia Research 24 (2000) 91–93 93

cells are inappropriately activated and up-regulated, soas to present self-antigens to the immune system. Thisleads to B-cell hyperplasia with abnormal antibodyproduction, and genetic error causing neoplasia [18].

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