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A 34 year old man with bilateral anterior uveitis and a rash

BMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d6831 (Published 31 October 2011) Cite this as: BMJ 2011;343:d6831
  1. Anish N Bhuva, foundation year 1, respiratory medicine1,
  2. Harpreet K Lota, specialty trainee year 3, respiratory medicine1
  1. 1Hillingdon Hospital NHS Foundation Trust, Uxbridge UB8 3NN, UK
  1. Correspondence to: H K Lota harpreet.lota{at}hotmail.co.uk

A 34 year old railway engineer of south Indian descent was under the care of the ophthalmology team. He was being treated for bilateral anterior uveitis with topical steroids and mydriatics after a one month history of decreasing visual acuity, photophobia, and ocular pain. He also had a four month history of irritation over his tattoo sites that his general practitioner had suspected was dermatitis related to ultraviolet radiation. He was also having severe night sweats. In view of these symptoms, he was referred to the medical team.

His medical history included well controlled asthma and two hospital admissions for lower respiratory tract infections in the past five years. He had no known allergies and the only drug that he took regularly was budesonide/formoterol 200/6. He was an ex-smoker, having stopped two months previously.

On admission, his observations were normal. Abnormalities over his tattoo sites were noted (fig 1) and his visual acuity was reduced to 6/18 bilaterally. All other systems examinations were normal. Full blood count, electrolytes, liver function tests, and bone profile tests were within normal ranges. C reactive protein was 13 mg/L (reference range 0-5) and his erythrocyte sedimentation rate was 14 mm in the first hour (0-10). Autoimmune serologies, VDRL, and HLA B27 were negative. Serum angiotensin converting enzyme was 154 mg/L (20-90). A chest radiograph was performed (fig 2).

Figure1

Fig 1 Abnormalities over the patient’s tattoo sites

Questions

  • 1 What abnormalities can be seen in the figures?

  • 2 What is the likely diagnosis?

  • 3 How else does this condition present?

  • 4 How would you manage a patient with this condition?

Answers

1 What abnormalities can be seen in the figures?

Short answer

The tattoo has a raised indurated appearance over the surface of the pigment (fig 3). The chest radiograph shows bilateral hilar lymphadenopathy (fig 4).

Figure3

Fig 3 Induration over the surface of the pigment in the patient’s tattoo (arrows)

Figure4

Fig 4 Chest radiograph showing bilateral hilar lymphadenopathy (arrows)

Long answer

The loss of the normal concave shape of each hilum suggests that the patient has bilateral hilar lymphadenopathy. Each hilum consists of lymph nodes and pulmonary vasculature, and either can contribute to enlargement. The lobular appearance at each hilum is indicative of lymphadenopathy rather than vascular enlargement, which typically has a smoother outline.

2 What is the likely diagnosis?

Short answer

The combination of anterior uveitis, rash, and bilateral hilar lymphadenopathy can be caused by sarcoidosis, mycobacterial infection, or lymphoma, but the most likely diagnosis is sarcoidosis. The pathognomonic feature is the reaction within the patient’s tattoos, which would not occur with the other differential diagnoses. It is caused by the accumulation of non-caseating granulomas—the pathophysiological end feature of sarcoidosis.

Long answer

A clinician presented with this combination of symptoms would need to consider lymphoma and mycobacterial infection. However, the pathognomonic feature that raises the suspicion of sarcoidosis is the infiltration of the tattoo sites.

Sarcoidosis is a multisystemic granulomatous disease that mostly affects young to middle aged adults.1 2 The name comes from its original description as a “benign sarcoma of the skin.”3 The causes are unknown, but because it mainly affects the lungs, eyes, and skin, environmental antigens are thought to have a role.1 4 These include inorganic and organic particles such as cadmium in tattoo ink,5 aluminium, talc, zirconium, insecticides, and mould. There is a weak association with agricultural work.6 Several infectious organisms have also been postulated, including viruses (herpes family, retrovirus, coxsackie B virus), mycobacteria, proprionibacteria, and mycoplasma.1 Human HLA alleles are also associated with increased risk and phenotype.4 Although the mechanism is still unclear, a genetic predisposition probably causes susceptibility to the environmental antigen.1 4

3 How else does this condition present?

Short answer

Sarcoidosis is unusual in that it can affect any organ. A common acute presentation (9-34%) is Lofgren’s syndrome, which consists of erythema nodosum, arthralgia, and bilateral hilar lymphadenopathy. A similar proportion of patients present with respiratory symptoms (including wheeze) or incidental findings on chest radiography. Sarcoidosis should also be considered in patients with unexplained neurological and cardiac symptoms because it can potentially have a fatal outcome.

Long answer

Because sarcoidosis is a multisystem disease, it can present with a range of symptoms depending on the organ affected.1 2 4 The pattern of presentation is influenced by sex and ethnicity; for example, Lofgren’s syndrome is more likely to present with erythema nodosum in women and arthralgia alone in men. It is roughly three times more common in African-Americans than in white Americans, and it is more likely to be chronic and severe in this group.

Around 90% of cases present with lung symptoms.2 Shortness of breath, cough, and wheeze are common. The first line investigation is a chest radiograph, which can be used to stage the disease (table). Our patient had bilateral hilar lymphadenopathy, indicating stage 1 disease.

Staging of sarcoidosis*

View this table:

When taken together with the clinical symptoms, high resolution computed tomography can show typical features and enable a diagnosis to be made without the need for biopsy. Although non-specific, these include nodules, irregular linear opacities, ground glass shadowing, air trapping, and fibrosis. It can also identify complications such as bronchiectasis, aspergilloma, and fibrobullous disease.2

Sarcoidosis can affect any part of the eye, and 25-80% of patients present with eye problems.2 It commonly presents as chronic anterior uveitis and may cause glaucoma, cataracts, and visual loss.

The skin is affected in about 24% of patients, with erythema nodosum and lupus pernio being the most well known manifestations. Lupus pernio describes indurated violaceous plaques on the cheeks, nose, lips, or ears. Infiltration of tattoo sites has been noted since 1955; it is associated with pulmonary sarcoidosis and often has a long latency period.9 An isolated tattoo rash can provide an accessible biopsy target. It typically shows non-caseating granuloma without organisms or particles, but this is not specific to sarcoidosis.2

Around 5% of patients have neurological symptoms,2 most commonly cranial nerve palsies, which often involve the facial nerve. Other symptoms include headache, cognitive dysfunction, weakness, and seizures. Any new symptom suggesting inflammation of the central nervous system demands prompt investigation.

Although rare (only 2% of patients),2 cardiac sarcoidosis is associated with the highest mortality. Any new symptom that suggests cardiac involvement should therefore be assessed, ideally with a combination of Holter monitoring, echocardiography, and gadolinium enhanced magnetic resonance imaging. If clinical suspicion is not confirmed, electrophysiological studies should be considered.

Lymphadenopathy is a common occurrence. Hypercalcaemia may occur owing to the ability of granuloma macrophages to activate 25-hydroxyvitamin D3 via 1-hydroxylation. This can lead to nephrocalcinosis, which may be severe enough to cause renal failure. Liver enzymes may be raised, although this is rarely clinically significant.

4 How would you manage a patient with this condition?

Short answer

Because the remission rate is high, only patients with symptomatic or organ threatening sarcoidosis require treatment. Prednisolone is the recommended treatment, at a starting dose of 0.5 mg/kg/day for four weeks, but higher doses may be needed for cardiac sarcoidosis or neurosarcoidosis. It can be reduced to a maintenance dose and should be continued for several months before re-evaluation.

Long answer

After the acute episode, management involves assessment and surveillance of multi-organ involvement for at least two years after diagnosis.1 Assess baseline liver function, serum and urinary calcium, and lung function and carry out electrocardiography.10 Complete neurological and ophthalmology examinations should be performed with appropriate specialist referral as indicated. A slit lamp examination is necessary to detect asymptomatic posterior uveitis.2

The measurement of serum angiotensin converting enzyme and the Kveim test have historically been used when investigating suspected sarcoidosis. Measurement of serum angiotensin converting enzyme has 60% sensitivity but low specificity because it is also raised in tuberculosis and lymphoma. British Thoracic Society guidelines suggest it has a limited role in diagnosis and does not add to lung function and imaging when monitoring pulmonary disease,10 although it may be appropriate in individual patients to monitor disease activity. Possible serum markers including tumour necrosis factor receptor II have been proposed.11 The Kveim test involves an intradermal injection of homogenised human sarcoid tissue extract. Although it has 50% sensitivity and close to 100% specificity, because of the impracticality of using human tissue the test is no longer used.

Patients who are free of symptoms or signs of progressive disease on serial lung function tests or chest radiography do not generally require treatment. For those with symptomatic or progressive disease, oral corticosteroids are first line treatment. Absolute indications for corticosteroids include hypercalcaemia and neurological, cardiac, or ocular symptoms (if topical treatment fails).2 High quality evidence for the use of steroid sparing agents is limited, and these tend to be used under expert guidance when corticosteroids are ineffective or have intolerable side effects.2 4 10 Methotrexate is normally the treatment of choice,10 and because tumour necrosis factor has a role in granuloma formation, biological inhibitors can be considered.4 10

Patient outcome

Two months into treatment, our patient’s eyesight had improved and the changes to the tattoo site had resolved. Unfortunately, as the steroid dose was reduced the inflammation at the tattoo site began to recur. The patient therefore is continuing to receive low dose maintenance steroids.

Notes

Cite this as: BMJ 2011;343:d6831

Footnotes

  • All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References

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