Case #038

Bilateral hilar lymphadenopathy, erythema nodosum, ankle arthritis and fever together are Löfgren syndrome, the acute face of sarcoidosis, and the combination is specific enough that biopsy is sometimes not needed at all. The work of the case is excluding the two conditions that produce hilar nodes and granulomas and are treated in the opposite way. Tuberculosis is the first: its granulomas are caseating, with cheesy necrosis at the centre, whereas these are well formed and necrosis-free, and the negative Ziehl–Neelsen, culture and interferon-gamma release assay close it off. That distinction is not academic, since the treatment for sarcoidosis is corticosteroids, which would be actively dangerous in untreated tuberculosis. Lymphoma is the second, and the symmetry argues against it: lymphoma tends to produce asymmetrical, bulky mediastinal disease rather than mirror-image hilar nodes with clear lungs. The remaining numbers fit the mechanism. Lymphopenia is characteristic, because T cells are sequestered into the affected tissue rather than depleted. The hypercalcaemia comes from granuloma macrophages expressing 1α-hydroxylase and converting vitamin D to its active form outside normal feedback control, which is also why these patients are told to avoid supplements and strong sun. Serum ACE is produced by the granulomas themselves; it is too insensitive and non-specific to diagnose on, but it fits. Löfgren syndrome carries the best prognosis of any sarcoid presentation, most cases remitting within two years, which is why much of sarcoidosis needs no treatment at all and non-steroidal anti-inflammatories would ordinarily cover the arthritis and the erythema nodosum. What changes the calculation here is the calcium of 2.78 mmol/L. Hypercalcaemia is a recognised indication to treat, alongside progressive lung disease, cardiac or neurological involvement and eye disease, so she gets oral prednisolone at moderate dose, tapered over six to twelve months, with methotrexate as the usual steroid-sparing second line.