This case highlights a rare localisation of TB, without pulmonary or other organs involvement, in a chronic immunosuppressed host. Prior to transplant, a detailed anamnesis is necessary to estimate the risk of LTBI and/or active TB. In fact, even if our patient was born and raised in a low TB prevalence country, he lived and worked for several years, in high TB prevalence nations .
Subsequently screening for latent TB in patients undergoing OLT and other solid organ-transplant (SOT) is mandatory to assess the risk of developing active-TB and planning LTBI treatment or prophylaxis [7, 8]. As suggested by Zenner et al., either TST or IGRA-test may be used to annually monitor candidates to SOT . In this case, the patient had a positive IGRA-test and, although drug related toxicity may be a concern, the benefit of LTBI treatment in a host undergoing chronic-immunosuppression should drive the choice. Furthermore, a 3 months isoniazid-rifampicin dual regimen has been proven to be safe and efficient . Unfortunately, due to fear of liver toxicity and possible drug-drug interactions, treatment of LTBI before and after SOT was postponed.
Although CTB diagnosis is often overlooked due to the variety of possible differential diagnosis, the molecular diagnostic tools for TB detection approved by WHO, remarkably reduce time to diagnosis and are both sensitive and specific [11, 12].
CTB often represents the haematogenous or lymphatic spread of MTB from other foci therefore, treatment of sensible CTB follows the same rules of TB of other organs with an intensive phase of 2 months with isoniazid, rifampicin, ethambutol and pyrazinamide followed by a maintenance phase of 4 months with isoniazid and rifampicin. Thus, when CTB is suspected, a diagnostic approach aimed to exclude internal organ involvement, especially PTB, is mandatory.
Rarely CTB is confined as only cutaneous, probably for direct inoculation of MTB, like in the case of tuberculosis verrucosa cutis and lupus vulgaris: these forms of CTB are not associated with internal organ involvement but, the length and the regimen of sensible MTB treatment remain the same .
Treatment with rifabutin was initiated to decrease the chance of drug to drug interactions due to the use of molecules which share the same cytochrome P 450 (CYP450) metabolic pathway. Rifampicin is a metabolic inducer of CYP450 and may decrease calcineurin inhibitors haematic level [13, 14]. Rifabutin, as a milder inducer of CYP450, may have a lower impact on both calcineurin inhibitors then rifampicin . Therefore, according to previous studies that compared rifamycins in TB treatment, rifabutin was started along with careful monitoring of both tacrolimus and everolimus in order to decrease the likelihood of modifications in calcineurin inhibitors haematic level [15,16,17,18].
A clinical relevant reduction in tacrolimus and everolimus blood levels was then expected, but the extent was not predictable . In addition, all drugs used for the CTB are known to potentially cause liver toxicity, undermining the treatment tolerability, OLT and clinical outcome. However, different reports described efficacy and safety of rifabutin in treating TB patients who presented allergy to rifampicin or potential harmful drug-drug interactions .
Finally, cost-effectiveness of TB screening is also an important issue. In Italy different protocols are in use to screen categories at risk. TST is often used as first screening because of the very low cost and in some referral medical centres positive cases are confirmed by IGRAs. IGRAs sensitivity has been reported higher then TST in several studies in HIV infected individuals . In any case the intention to test should be linked to the intention to treat or, if treatment is not possible, to monitor the patient, particularly if the immunity is impaired.
As suggested by the TBNET consensus, treatment of LTBI in transplant candidates and after SOT should be offered according to national guidelines, thus reflecting regional drug availability and resistance patterns . However, if LTBI treatment is not possible both during pre-transplant phase and in the post-transplant phase, close monitoring of signs and symptoms of active TB is recommended . In patients undergoing SOT in low TB prevalence countries, careful anamnesis, TB risk factors assessment and LTBI screening are recommended. Although a rare presentation of active TB, due to the plethora of cutaneous presentation, CTB should be suspected in immune-compromised host.
Molecular tests and classical microbiological investigations on bioptic specimen are helpful tools to facilitate correct diagnosis of CTB.