F
Nelson and G A McKay
University
Medical Unit, Wards 29 & 30, Glasgow Royal Infirmary, Castle Street,
Glasgow, G4 0SF
Author
for correspondence:
Dr
Gerard McKay, Consultant Physician, University Medical Unit, Wards 29 & 30,
Glasgow Royal Infirmary, Castle Street, Glasgow, G4 0SF, UK
E-mail:
gerard.mckay@ggc.scot.nhs.uk
SMJ 2009 54(1): 58
Abstract
A 40-year-old female who was an ex-intravenous drug user on methadone
presented to the Emergency department reporting all over body pain and was
subsequently found to have a diagnosis of non-Hodgkin’s B cell lymphoma in the
absence of lymphadenopathy. She did not respond to chemotherapy and pain
management was difficult. This case demonstrates three things. Firstly,
clinicians should be aware that ex- or current intravenous drug users presenting
with pain may have significant pathology. Secondly, pain management in patients
on methadone can be difficult. Lastly, the case describes an atypical but
recognised presentation of lymphoma with bone involvement but no lymphadenopathy.
Case
history
A
40-year-old female presented to the Emergency department reporting all over body
pain that was aching in nature and maximal at her hip and shoulder joints.
The pain was so severe that she reported difficulty with breathing and
being unable to mobilise. There was associated reduced appetite. She had a past
medical history of intravenous heroin use but she had not injected for 2½ years
and on admission was taking 120ml Methadone daily. She was known to be hepatitis
C antibody positive, had an ileostomy for severe chronic constipation and had
previously been diagnosed with severe depression. She smoked 15 cigarettes a
day, did not drink alcohol and was unemployed.
Her symptoms were so disabling in the month leading up to her admission
that her family had been doing her housework and shopping.
She
had been admitted to hospital one week previously and patchy changes noted
bi-basally on her chest x-ray. On that admission pain was a prominent symptom,
which was thought likely to be a consequence of a presumed atypical pneumonia
and was discharged to complete a course of antibiotics. On her re-presentation
the patient was drowsy, had a blunted affect, but was orientated.
All observations were within normal limits.
Cardiovascular, respiratory, abdominal, lymph node and breast
examinations were all normal. There
was reduced power in both upper limbs; power was rated 4/5 in both shoulders.
The remainder of the neurological examination was normal. All joints were
tender to touch and movement limited by pain.
The left hip joint and both elbows and shoulders were most severely
affected. There was also discomfort on palpation of the ribs anteriorly and
posteriorly.
Blood
tests found the following abnormalities: Haemoglobin 10.8g/dL, CRP 169mg/L, ESR
104mm/hr GGT 333U/L, Alk Phos 266U/L, Alb 27g/L, PO4 1.78mmol/L, Ad Ca
2.64mmol/L, Ddimers 4655IU, Hepatitis C virus antibody positive and IgG 18.8g/L.
Chest
X-ray was normal. Abdominal
ultrasound noted mildly enlarged spleen and nil else of concern.
CT chest, abdomen and pelvis were requested to exclude an underlying
malignancy. CT abdomen noted
grossly abnormal bones throughout the axial skeleton with rib fractures and the
presence of lytic deposits in the ribs, spine and pelvis.
NM
bone scan detected multiple hot spots in the skull, spine, rib cage, shoulder
joints, left neck of humerus, pelvis and the upper third of both femur and
sternum (see figure 1). Bone marrow
aspirate and trephine biopsy were performed and confirmed a diagnosis of diffuse
large B cell lymphoma.
Figure
1. Bone Density Scan showing
multiple hot spots (PLEASE INSERT FIGURE HERE)
She
was then transferred to a specialist oncology centre but did not respond to an
initial course of chemotherapy and subsequently went on to receive palliative
care in a hospice. Pain management
proved to be a challenge. In
addition to 120ml Methadone once daily, her pain was managed by Paracetamol,
Ibuprofen and 10mg Oromorph as required. The
patient continued to experience severe pain and in view of the patients
ileostomy it was considered that she may not have been adequately absorbing the
above analgesia. A 12microgram
fentanyl patch was therefore added to reduce the need for breakthrough
analgesia. Unfortunately breakthrough oromorph requirements continued to
be up to 70mg per day. The
appropriate opioid conversion was calculated and a 25microgram fentanyl patch
was administered.
When
patients who are ex- or current intravenous drug users present with severe pain
it is often considered to be opiate seeking behaviour.1 This may
explain our patient’s delay in presenting to secondary care and initial label
as musculoskeletal chest pain in association with pneumonia despite the longer
history of disabling symptoms. Clinicians should be aware that this, often
difficult, group of patients to manage can have significant underlying diagnosis
and opiate seeking behaviour should be a diagnosis by exclusion.
Research has found that the experience of pain in those addicted to
opioids may be heightened when compared to that experienced by control subjects
resulting in under treatment and consequently, suboptimal medical management.2
Even
when we had established the diagnosis of non-Hodgkin’s lymphoma pain
management was complicated and she benefited from the multi-disciplinary
approach offered by the palliative care team.
Non-hodgkin’s
lymphoma predominantly presents in patients of 40 years and older.
A variety of presenting symptoms have been recognised, the most common of
which is painless lymphadenopathy. Systemic
symptoms, defined as ‘B’ symptoms can include fever, malaise and weight
loss. Bone marrow infiltration may
occur, however this usually occurs in the presence of lymphadenopathy.
Primary bone lymphoma has been described but is an uncommon finding.
Horsman
et al carried out a retrospective review of all patients presenting to the
Sheffield Lymphoma Group.3 3148
cases of Lymphoma had been diagnosed over a 34 year period, and of these 37
patients (1.2%) had unequivocal bone lymphoma.
In this patient group the predominant presenting symptom was bone pain
with the pelvis being the most common site.
70.3% of these patients had diffuse large B cell lymphoma.
This study found that bone lymphoma has a better prognosis than other
extranodal lymphomas, with complete response and younger age being favourable
markers.
Nakamura
et al described 5 cases of CD5+ diffuse large B cell lymphoma presenting with
bone marrow involvement and the absence of lymphadenopathy.4
The 5 patients studied presented with fever and general fatigue.
Diagnoses of Lymphoma were made from bone marrow aspiration and at no
point did any of these patients exhibit lymphadenopathy.
Of the 5 patients studied 4 died of their disease, time from diagnosis to
death ranged from 1 month to 23 months. At
the time of reporting one patient was still alive and in complete remission.
In
addition to the unusual presentation of our patient’s lymphoma, it is also of
interest that she is hepatitis C virus (HCV) antibody positive.
Hepatitis C infection has been found to play a part in the pathogenesis
of mixed cryoglobulinaemia, encouraging the stimulation and expansion of B
cells. It has been found that
treating the viral infection can lead to a resolution of the cryoglobulinaemia
in some patients. In some forms of
low grade non-hodgkin’s lymphoma, clearance of HCV may result in remission of
the neoplasm. Despite remission
being uncommon with aggressive lymphomas there may still be benefit in treating
HCV as a means of reducing chemotherapy related hepatotoxicity.5 Our
patient’s treatment was palliative and therefore she did not have her
hepatitis C actively treated.
In
conclusion this case demonstrates three things.
Firstly, clinicians should be aware that ex- or current intravenous drug
users presenting with pain may have significant pathology. Secondly, pain management in patients on methadone can be
difficult. Lastly, the case
describes an atypical but recognised presentation of lymphoma with bone
involvement but no lymphadenopathy.
References
1. Dunn KE, Sigmon SC et al. Evaluation of Ongoing Oxycodone Abuse Among Methadone-Maintained Patients. Journal of Substance Abuse Treatment. 2008 Feb 21
2. Afford D, Compton P, Peggy RN, Samet J. Acute Pain Management forPatients Receiving Maintanance Methadone or Buprenorphine Therapy. Annals of Internal Medicine. Volume 144, 17 January 2006, pp 127-134
3. Horsman, JM. Thomas, J. Hough, R. Hancock, BW. Primary Bone Lymphoma: A Retrospective Analysis. YCR Academic Unit of Clinical Oncology, Western Park Hospital, Sheffield, UK. International Journal of Oncology 28: 1571-1575, 2006
4. Nakamura, Naoya. Kuze, Tutsuo. Hashimoto, Yuko et al. CD5-Positive Diffuse Large B-Cell Lymphoma Presenting in Bone Marrow without Lymphadenopathy. Department of Pathology. Internal Medicine, Fukishima Medical University School of Medicine, Fukishima. Iwaki Kyoritsu General Hospital, Iwaki. Ohta-Nishinouchi General hospital, Koryama. Journal of Clinical and Experimental Hematopathology Vol 41 No. 1. May 2001
5. Romero-Gomez M, Garcia-Romero D. Hepatitis C: Cryoglobulinaemia and non-Hodgkin Lymphoma. Rev Esp Enferm Dig: 100(3):164-170. Mar 2008