POEMS syndrome with pulmonary nocardiosis: A unique presentation

Sir,

We present a case of a 52-year-old man who presented with bilateral lung cavities, bone lesions and demyelinating polyneuropathy. This clinical picture raised a suspicion of a metastatic malignancy however on detailed workup he was diagnosed to have osteosclerotic myeloma (OM) with POEMS syndrome, a rare multisytem disorder comprising of conglomeration of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes.

A 52-year-old man non-smoker presented with 1 month history of fever, night sweats, cough with copious purulent sputum, dyspnea and constitutional symptoms. He also gave history of tingling numbness of both lower limbs for last 6 months and subsequently progressively increasing weakness in both lower extremities. He was a known diabetic since last 6 months. His vital parameters were stable. He had clubbng. Skin examination showed icthyosis and hyper pigmentation especially at upper and lower extremities and abdomen. Chest examination revealed bilateral crackles. Neurological examination showed reduced power (3/5) in lower limbs, impaired touch and pain sensation and decreased deep tendon reflexes. Laboratory studies showed anemia and elevated total counts with normal liver and renal function tests. ELISA test for human immunodeficiency virus (HIV) was negative. Sputum culture isolated nocardia while sputum smears and culture for acid fast bacilli were negative. Chest radiograph [Figure 1] showed bilateral lower zone cavities. Contrast-enhanced chest CT showed thick enhancing cavities in bilateral lower lobes with sclerotic bone lesions [Figure 2]. Electromyography (EMG) showed prolonged distal latency with low nerve conduction velocities and absent synaptic action potentials in bilateral tibial, sural and common peroneal nerves which suggested a demyelinating axonal peripheral neuropathy affecting the lower limbs.

Figure 1.

Chest radiograph showing bilateral lower zone cavitory lesions

Figure 2.

Contrast enhanced computerized tomography of chest showing thick enhancing cavitory lesions in bilateral lower lobes (L > R) with sclerotic bone lesions

Complete radiological survey revealed sclerotic lesions throughout the skeleton including the skull [Figure 3]. Because of this multisystemic involvement, we kept a differential diagnosis of metastatic malignancy versus POEMS syndrome with OM and accordingly did the further workup. A CT-guided biopsy of the lung lesion showed no evidence of malignancy. Bone marrow biopsy was normal. Serum and urine protein electrophoresis did not reveal a monoclonal protein. Hence, we decided to go ahead with serum and urine immunofixation. Simultaneously, the patient was started on therapy with antibiotic cotrimoxazole for nocardiosis. However, his clinical condition deteriorated and he expired. Histopathology of the chest lesion during a partial chest post mortem showed infectious process with special stains positive for nocardia. Urine immunofixation report was also available subsequently which showed monoclonal gammopathy of IgA type with lambda light chains. Our patient now satisfied all the criteria required for the diagnosis of POEMS syndrome. Hence, a final diagnosis of POEMS syndrome with OM with pulmonary nocardia infection was made.

Figure 3.

Radiograph of skull showing multiple sclerotic lesions

POEMS syndrome is a rare medical syndrome with multisystem involvement seen in setting of plasma cell dyscrasia. It usually manifests in the 5^th to 6^th decade of life. It affects twice as many men as women. It is postulated that proinflammatory cytokines especially vascular endothelial growth factor (VGEF) is responsible for the pathogenesis. The diagnostic criteria are proposed by Dispenzieri et al.[1] Mandatory major criteria include polyneuropathy (typically demyelinating), monoclonal plasma cell proliferative disorders (almost always λ), other major criteria include Castlemans disease, sclerotic bone lesions and elevated VEGF levels. Minor criteria include organomegaly, extra vascular volume overload, endocrinopathy, skin changes, papilloedema and thrombocytosis or polycythemia. Diagnosis is confirmed when both of mandatory major, one of other three major and one of six minor criteria are present.

Our patient fulfilled both the mandatory major criteria in form of demyelinating polyneuropathy, one other major criterion in the form of sclerotic bone lesions and minor criterion in the form of diabetes mellitus and skin changes. He thus satisfied all criteria required for diagnosis of POEMS syndrome. Finger clubbing was an associated feature. OM is a plasma cell dyscrasia characterized by sclerotic bone lesions and demyelinating polyneuropathy.[2] POEMS syndrome is most commonly associated with OM. In patients with OM, a monoclonal protein is present in serum or urine of 75% of patients. The identification of such a protein is usually a key to the diagnosis. The proteinuria can sometimes obscured by other proteins and immunofixation may be necessary for detection[3] as had happened in our case. M protein is usually IgG or IgA with lambda light chains and a bone marrow biopsy shows less than 5% increase in plasma cells or may be normal.[3] Radiologically OM is always associated with sclerotic lesions though lytic lesions may be present.[2]

Pulmonary manifestations of POEMS syndrome are common and include pulmonary hypertension, restrictive lung disease, respiratory muscle weakness, pleural effusions and diaphragmatic elevation as shown in a retrospective review conducted over 137 patients by Allam et al.[4] Our patient presented with the pulmonary manifestation of bilateral lung cavities, which were however due to Nocardia infection. Nocardiosis is an important opportunistic disease that can manifest as localized or disseminated infection. It tends to affect patients with underlying immunosuppression.[5] Patients with hematological disorders are a high-risk category for nocardiosis because of intrinsic immunodeficiency.[5] In our patient POEMS syndrome produced a disturbance in the immune system, hence pulmonary nocardiosis seems secondary to this. Pulmonary system is the most commonly involved organ system, infection being acquired by inhalation of airborne spores. It usually presents as nodular or escavated lesions.[5] Our patient also presented with multiple lung abscesses. Diagnosis is by demonstration of organism in smear and isolation by culture with modified Kinyon staining [Figure 4]. Sulphonamide group of antibiotics with or without trimethoprim have been regarded as the drug of choice. Prognosis in a patient with POEMS syndrome depends on the underlying plasma cell disorder. Prognosis is poor if effusions, ascites, edema or multiple lytic lesions are present. Cardio respiratory failure, renal failure, and infection are the common cause of death.[6] Our patient had developed a complication in form of pulmonary infection with nocardia manifesting as lung abscesses thereby accounting for his poor prognosis and mortality.

Figure 4.

Histopathology of a chest lesion with special stains demonstrating Nocardia

POEMS syndrome is a distinct entity with diverse clinical manifestations and multisystem involvement. Hence, we emphasize that patients with multisystem involvement and peripheral neuropathy should be evaluated with serum and urine protein electrophoresis and if necessary immunefixation as the importance of recognizing this rare disease lies in its potential for treatment. We also stress that patient with POEMS syndrome may suffer from pulmonary nocardiosis due to underlying immunosuppression and whose outcome may be fatal. This case is thus unique by its rare pulmonary manifestation and close resemblance to malignancy. It serves to remind the clinician to consider this syndrome whenever confronted with such a case presenting with multisystem involvement. Early diagnosis and therapy are crucial.