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Dear colleague, Could I ask you to see my patient, Patient A? She is 24-years-old and has just transferred to the practice, having had some issues with her previous general practitioner. Her main complaints are chronic muscle and joint pain. All muscle groups are involved, but her shoulders and back seem to be the worst areas affected. There is no clear history of joint swelling and, on examination, no deformities or synovitis. She has been troubled by these pains since adolescence, though she informed me she was a keen gymnast at school. The other concerning issue is severe fatigue. This dates from a holiday in Spain last summer when she apparently developed a febrile illness, precipitating her early return, at which time she also split up from her long-term boyfriend. She now has very poor exercise tolerance, becoming fatigued and dizzy after walking for more than 10 minutes on the flat, and has been off work (she is a university administrative assistant) for the last 3 months, and indicated that she is quite likely to lose her job. I have accessed her previous records, and I note that she was investigated for an irregular bowel habit while at college, but a faecal calprotectin and other tests were normal, and a putative diagnosis of irritable bowel syndrome was made. This problem seems to have settled. While at school, she was also investigated for a chronic headache, attributed then to excessive screen use. Computed tomography of the brain was normal, and she is no longer under neurological follow-up. Current medications include etoricoxib, 60 mg once per day, and nortriptyline, 50 mg nocte. She also takes co-codamol, one tablet three times per day, prescribed by a colleague, but does, I think, obtain additional supplies from an online pharmacy, which is clearly a matter of concern. She does not feel that any of these medications really help her pain. I have been reluctant to start gabapentin, or anything similar, in the absence of a clearer diagnosis. I have performed some baseline blood tests: full blood count, urea and electrolytes, and thyroid function tests are normal; C-reactive protein <5 mg/L; rheumatoid factor was negative. Many thanks for your help, Yours etc - Box 2.
Possible response to the potential referral letter to the rheumatology clinic in Box 1; Dr A
Dear Doctor, re Patient A Thank you for your helpful letter about Patient A. The referral was triaged through the regional referral management service to our EA (early arthritis) clinic and I reviewed her this week. The history is as you described, with a long history of ill-defined musculoskeletal pain. On examination, there was no evidence of either inflammatory or degenerative arthritis. I note the normal blood count results, low C-reactive protein and negative latex test. I think we can be confident that this patient does not have a serious musculoskeletal condition. In particular, there is nothing to suggest rheumatoid arthritis, a seronegative arthritis or lupus. I was able to reassure her that this was the case, and I have discharged her from the clinic. Yours etc - Box 3.
Possible response to the potential referral letter to the rheumatology clinic in Box 1; Dr B
Dear Doctor, re Patient A Thank you for your helpful letter about Patient A. The referral was triaged through the regional referral management service to our EA (early arthritis) clinic and I reviewed her on my consultant's behalf today. I took the opportunity to review her history in some detail. I note the previous history of gastrointestinal upset and headaches. She was also unwell with a short febrile illness while on holiday last year. As you note, she has widespread muscle pain and marked fatigue, and she also told me that she had had two aphthous mouth ulcers in the last year. Patient A also informed me that she was seen some years ago by Prof Y in London, who suggested the possibility of antinuclear antibody-negative lupus. I think we need to exclude the possibility that she has inflammatory bowel disease and an associated seronegative arthritis. The headaches also raise the possibility of anti-phospholipid syndrome (a common cause of migrainous headaches in young women), or indeed systemic lupus erythematosus. The latter may, of course, cause myositis, which may be the explanation for her muscle pain. The recent febrile illness is also a matter of concern, and Lyme disease, acute cytomegalovirus, Epstein–Barr virus or parvovirus are clearly possibilities. Parvovirus infection is, of course, not infrequently complicated by chronic arthritis. I have therefore arranged for a repeat blood count, urea and electrolytes, and a full auto-antibody profile, including antinuclear antibodies, extractable nuclear antigen, anti-cardiolipin testing, anti-neutrophil cytoplasm antibodies, anti-tissue transglutaminase and Anti-C1q antibodies, as well a full panel of myositis-specific antibodies, including anti-Jo1 antibodies to exclude anti-synthetase syndrome. I am also checking her HLA-B27 status, and also for HLA-B51, to exclude Behçet's disease, in light of the mouth ulceration. In addition, I have put in train magnetic resonance imaging of her brain and also spinal and sacro-iliac joint magnetic resonance imaging, and requested electromyography and nerve conduction studies. I have arranged to review her to discuss the blood test results in around 3 weeks, and then again to review the imaging and electrophysiological testing in 3 months’ time (there is a considerable wait for these tests at present). If the diagnosis is still unclear at that point, I will consider a positron emission tomography – computed tomography, which is often useful in the setting of undiagnosed inflammatory conditions, such as Takayasu's arteritis. Yours etc - Box 4.
Possible response to the potential referral letter to the rheumatology clinic in Box 1; Dr C
Dear Doctor, re Patient A Thank you for your helpful letter about Patient A. I saw her in my multidisciplinary rheumatology new patient clinic this week. Reviewing her history, the active clinical problems today are widespread muscle pain and sensitivity, extreme fatigue and poor exercise tolerance, limited mainly by lack of energy, but also by a feeling of dizziness. This last symptom has bothered her for many years, and she has had a number of ‘faints’, one of which resulted, 2 years ago, in a visit to the emergency department. At which point, she had electrocardiography which showed a sinus tachycardia, but no other abnormality. The illness you mention is Spain sounds very much like an attack of holiday diarrhoea. She still experiences occasional intestinal hurry, but this is usually associated with the use of over-the-counter proton pump inhibitors, which she uses regularly on an as needed basis. Since she was investigated in her teens, she has had only occasional headaches, but she does complain of poor concentration and ‘brain fog’. She sleeps poorly, and wakes feeling unrefreshed. Due to her fatigue, she often sleeps for short periods in the day. Patient A also describes having a dry mouth, much worse since starting treatment with nortriptyline, but no ocular sicca, and only a very occasional mouth ulcer. Her weight is stable, and appetite fair. As you note, she has been off work for some time, and she was informed that an occupational health review is pending, something about which she is understandably very concerned. She does not have a regular partner at present and is not sexually active. On examination, Patient A looked well, but came across as very anxious. She was able to give a very good account of herself and brought along copies of a number of letters from specialists she had seen in the past. There was no lymphadenopathy, clubbing or rash, and a Shirmer's test was normal. Her resting pulse rate was 98 beats per minute, blood pressure (prone) 130/90 mmHg; blood pressure (standing) 100/70 mmHg. Cardiovascular, respiratory and abdominal examinations were all otherwise normal. Reflexes were brisk and symmetrical, with no evidence of a peripheral neuropathy or radiculopathy and, with encouragement, normal power in all muscle groups. Musculoskeletal examination revealed no joint deformity or swelling, a good range of back movement and no evidence of sacroiliac pathology. However, Patient A is clearly a hypermobile individual: Beighton score = 9, with markedly hyperextensible knees and elbow joints in particular. There was localised pain and tenderness referable to the parasternal area bilaterally, both elbows, buttocks and the muscles of the shoulders and neck on both sides. My view is that this patient has fibromyalgia, in association with anxiety, hypermobility and autonomic dysfunction (manifest as postural orthostatic tachycardia syndrome (PoTS)), ie FAHA. Many features in the history and examination support this diagnosis, notably the non-restorative sleep pattern and fatigue, widespread pain, and previous history of irritable bowel syndrome, ‘brain fog’ and headaches. I am rechecking her blood count and thyroid function tests, as well as calcium, magnesium (low magnesium is common in proton pump inhibitor (PPI) users) and vitamin D levels. No other blood tests or imaging are required. I shall discuss the results with her as part of a planned telephone follow up in 3 weeks. My colleague Dr D also reviewed the patient in our multidisciplinary clinic, and she was also assessed by our speciality physiotherapist, who is planning a graded exercise programme, and has referred her to our nurse-led fibromyalgia support group for advice on pain-management in particular. Dr D's letter is appended. I explained the clinical problem to Patient A, particularly the relevance of her hypermobility, and provided her with the Versus Arthritis information leaflets on both hypermobility and fibromyalgia, as well as a number of links to informative websites, with a view to discussing any specific issues at our future telephone consultation. We agreed to cease her PPI use, aim to reduce and stop her opiates, and also her etoricoxib in due course. I would recommend continuing nortriptyline for the time being and you may also wish to consider melatonin, 2 mg nocte for 2 months or so to try to normalise her sleep pattern. I have also agreed, with appropriate consent, to provide a report for the occupational health department at the university. Yours etc - Box 5.
Possible response to the potential referral letter to the rheumatology clinic in Box 1; Dr D
Dear Doctor, re Patient A I reviewed Patient A in our multidisciplinary clinic from a liaison psychiatry perspective. As Dr C suggests, there is a complex interplay between her physical symptoms which are likely unified by hypermobility. She reports, as is often found in similar presentations, a degree of anxiety with panic symptoms and some issues relating to her change in circumstances and impact of physical symptoms on mental health. She is going to engage with our physiotherapist to improve strength and stability with the hope of reducing pain and fatigue. Given her psychological symptoms and the symptoms suggestive of orthostatic intolerance (again very common in hypermobile presentations), I would suggest a trial of a low-dose beta blocker (providing no contraindications) to manage both anxiety and dysautonomic symptoms. She will likely benefit from a biopsychosocial approach, so I am referring her to our health psychologist and also signposting Patient A for vocational support and advice regarding reasonable adjustments and additional support to help her remain in work. Yours etc Clinical feature or abnormal test Other features Corroborative tests Differential diagnoses Serostis Documented fever or arthropathy CRP, FBC or genetic testing Familial Mediterranean fever Mucosal ulcers (oral/genital) Arthropathy, pathergy or rash/EN HLA-B51 Behçet's disease Sicca: oral/ocular Arthropathy or chronic rash Shirmer's test or auto-antibodies Sjogren's syndrome Osmotic symptoms Weight loss or abdominal pain Glucose, HbA1c or calcium Diabetes or hypercalcaemia Arthropathy Photosensitivity, Raynaud's syndrome or rash ANA, ENA, complement or ferritin Lupus, adult Still's disease or Lyme disease Urticaria >48 hours or residual discolouration ANA, anti-C1q Ab or complement Urticarial vasculitis (HUVS) Abdominal/pelvic pain Dyspareunia, menorrhagia or infertility Pelvic imaging or laparoscopy Endometriosis or Crohn's disease Extreme daytime somnolence Snoring, obesity or airway issues Specialist sleep study Obstructive sleep apnoea Lymphopenia EN, lupus symptoms or infections SACE, ANA or HIV testing Sarcoid, lupus or HIV ANA = antinuclear antibodies; CRP = C-reactive protein; EN = erythema nodosum; ENA = extractable nuclear antigen; FBC = full blood count; HbA1c = glycated haemoglobin; HUVS = hypocomplementemic urticarial vasculitis syndrome; SACE = serum angiotensin-converting enzyme.
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The challenges of chronic pain and fatigue
