A case of acquired partial lipodystrophy associated with POEMS syndrome

P. Caramaschi, D. Biasi, M. Lestani1 and M. Chilosi1

Dipartimento di Medicina Clinica e Sperimentale and
1 Istituto di Istologia ed Anatomia Patologica, Università di Verona, Italy

SIR, A 45-yr-old woman presented with partial lipodystrophy (PL) at the age of 35 yr, characterized by the disappearance of fat at the cheeks, upper limbs and trunk. In 1996 she came to our observation; undifferentiated connective tissue disease was diagnosed on the basis of Raynaud's phenomenon, dry eyes, positivity of antinuclear antibodies (titre of 1:80 with speckled pattern), lupus anticoagulant and anticardiolipin of IgM class (9.9 U/ml). The physical examination revealed partial symmetric lipodystrophy, hypertrichosis and diffuse hyperpigmentation. Full blood count, erythrocyte sedimentation rate, transaminases, creatinine, glucose, insulin level, cholesterol, triglycerides, C3 and C4 levels and urinalysis were normal. Rheumatoid factor and anti-ENA antibodies were negative. A low M-component IgG lambda was observed (2 g/l). C3 nephritic factor (C3NeF) was negative. Schirmer's test was positive. Sialography, minor salivary gland biopsy, capillaroscopy, chest and oesophageal radiographs and pulmonary functioning test were all negative. The patient was given 6-methylprednisolone at 8 mg/day and acetylsalicylic acid at 100 mg/day. Two years later she complained of the appearance of morphoea at the right buttock. At that time the case was reported for the unusual association of acquired PL, undifferentiated connective tissue disease and localized scleroderma [1].

In 2000 the patient presented with peripheral neuropathy with symmetrical motor and sensory deficiency at the lower limbs, urinary incontinence, weight loss, mild dyspnoea on exertion and low back pain. The physical examination revealed both modest hepatomegaly and splenomegaly. Laboratory findings showed subclinical hypothyroidism (TSH, 10 mUI/l) and hyperprolactinaemia (44 µg/l), thrombocytosis (platelet count, 900 000/mm3) and polycythaemia (haemoglobin level, 16.9 g/dl; red blood cell count, 5.875x106/ml). The amount of M-component was stable. The tumour necrosis factor-{alpha} (TNF-{alpha}) level was slightly increased (10 pg/ml). The radiograph of the skeleton showed an area with the largest diameter of 6 cm at the left iliac ala of prevalent osteolytic type with sclerotic edges (Fig. 1Go). The histological examination of the bone marrow biopsy made at the right iliac crest showed trabecular bone thickening with large aggregates of monoclonal plasma cells. The histological examination of the osteolytic area revealed a massive infiltration of plasma cells. Pulmonary function testing showed a restrictive pattern due to strength deficiency of respiratory muscles.



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FIG. 1. Pelvic radiograph shows an area with the largest diameter of 6 cm at the left iliac ala of prevalent osteolytic type with sclerotic edges.

 
A POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal component, skin changes) was diagnosed. After radiotherapy on the lytic area and seven cycles of chemotherapy with melphalan and prednisone, low back pain and scleroderma lesion resolved, haemoglobin level normalized, platelet count decreased to 450 000/mm3 and monoclonal component to 1 g/l, and the lipodystrophy was less evident. The other clinical features remained stable.

POEMS syndrome is a multisystemic disorder [2] associated with plasma cell dyscrasia, which is typically represented by plasmocytoma or osteosclerotic myeloma. Plasma cell dyscrasia seems to play a central role in the development of the syndrome; in fact when a plasmacytoma is found, the treatment with surgery or radiotherapy dramatically improves all the clinical manifestations of the disease [3]. The clinical picture varies; endocrine disorders and skin manifestations may be very different, and in some cases of POEMS syndrome, thrombocytosis and polycythaemia have been reported [3].

Many patients with POEMS syndrome show high levels of interleukin 1ß (IL-1ß), TNF-{alpha} and IL-6 [4]. The alteration of the cytokine network, which may be responsible for some of the clinical manifestations such as endocrinopathy, skin changes, organomegaly and osteosclerosis [4], does not seem to account for the whole clinical picture; a relevant pathogenetic role may be played by the increase of vascular endothelial growth factor [5], which may be related to the histologically demonstrated microvascular alterations.

PL is a rare disorder of unknown aetiology. C3NeF is frequently detected in serum [6]. C3NeF represents an autoantibody of the IgG class which binds the alternative pathway C3 convertase causing continuous activation of C3 [7]. This immunological environment may predispose to viral infection and chronic immunocomplex production, favouring the development of both mesangiocapillary glomerulonephritis type II and autoimmune diseases [6].

To our knowledge the association of acquired PL with POEMS syndrome has never been reported. Our patient first developed PL and after 10 yr a typical picture of POEMS syndrome associated with thrombocytosis and polycythaemia. The pulmonary function tests may be compatible with phrenic nerve paresis, which is a rare manifestation among the broad clinical spectrum of the neurological involvement in POEMS syndrome [8].

Considering both the rarity of the two diseases and the large variety of their clinical pictures we think that a link between acquired PL and POEMS syndrome may exist. Hypertrichosis and skin hyperpigmentation, which were present at the time of our first observation, may be part of the clinical picture of both diseases. We do not know if the monoclonal gammopathy was present when PL was diagnosed; if so, it is possible that PL was the first clinical manifestation of POEMS syndrome and therefore it numbers among the large spectrum of skin changes in POEMS syndrome. The partial regression of lipodystrophy after chemotherapy may support this hypothesis.

This work was supported by a grant from Progetto Sanità, Fondazione Cassa di Risparmio di Verona, Vicenza, Belluno ed Ancona.

Notes

Correspondence to: P. Caramaschi, Dipartimento di Medicina Clinica e Sperimentale, Policlinico G. B. Rossi, P. le Scuro, 37134 Verona, Italy. E-mail: caramaschi{at}cmib.univr.it Back

References

  1. Biasi D, Caramaschi P, Carletto A, Bambara LM. A case of acquired partial lipodystrophy associated with localized scleroderma and undifferentiated connective tissue disease. Rheumatol Int 1999;19:75–6.[CrossRef][ISI][Medline]
  2. Crow RS. Peripheral neuritis in myelomatosis. Br Med J 1956;ii:802–4.
  3. Soubrier MJ, Dubost JJ, Sauvezie BJM and the French Study Group on POEMS Syndrome. POEMS Syndrome: a study of 25 cases and a review of the literature. Am J Med 1994;97:543–53.[ISI][Medline]
  4. Gherardi RK, Bélec L, Soubrier M et al. Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome. Blood 1996;87:1458–65.[Abstract/Free Full Text]
  5. Watanabe O, Maruyama I, Arimura K et al. Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in Crow–Fukase (POEMS) syndrome. Muscle Nerve 1998;21:1390–7.[CrossRef][ISI][Medline]
  6. Sissons JGP, West RJ, Fallows J et al. The complement abnormalities of lipodystrophy. N Engl J Med 1976;294:461–5.[Abstract]
  7. McLean RH, Siegel NJ, Kashgarian M. Activation of the classic complement pathway in patients with the C3 nephritic factor. Nephron 1980;25:57–64.[ISI][Medline]
  8. Mokhlesi B, Jain M. Pulmonary manifestations of POEMS syndrome. Case report and literature review. Chest 1999;115:1740–2.[Abstract/Free Full Text]
Accepted 16 August 2002





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