A new era of diagnostic modalities for type 1 leprosy reactions: Promise for the future

Type 1 reactions (T1R) are known to occur in upto 30 per cent of patients in the borderline spectrum of leprosy1. It indicates an unstable immunity in a patient. The reactions can be either upgrading, towards the tuberculoid pole or downgrading, towards the lepromatous pole. These may be purely cutaneous, neural or a combination of both2.

In early stages the diagnosis may be missed and hence, initiation of treatment delayed. This may have detrimental effects including permanent neurological sequlae. Though a thorough clinico-histological evaluation still remains the gold standard for diagnosis, various diagnostic assays are being used in research. These include cytokine mRNA levels, e.g. interferon-γ (IFN-γ), interleukin (IL)-1β, IL-2, IL-12, tumour necrosis factor α (TNFα) and enzyme-inducible nitric oxide synthase (iNOS)3. Previous studies indicate that potential biomarkers of T1R include CXCL10 and IL6 whereas IL7, platelet derived growth factor-BB (PDGF-BB) and IL6, may be markers of type 2 reaction (TR2)4.

Cytokine assays have been the focus of research in the recent past. The gene expression of CXCL10 and its receptor, CXCR3 has been the focus of several recent studies. CXCL10 is a chemokine induced primarily by IFN-γ, produced by macrophages, T cells, and keratinocytes. It causes recruitment of CXCR3+ cells into the tissue. CXCR3+ cells also release Th1 cytokines leading to further upregulation of CXCR3 ligands leading to T1R response and granuloma formation5. The expression of these cytokines is higher in type 1 reaction, in comparison to non-reactional skin biopsies throughout the whole spectrum of leprosy. However, serological assays at baseline and immediately before T1R have not been predictive4.

It has been seen that patients with high cytokine levels have a poor recovery from nerve function impairment during an acute episode of TIR6. They also have a high risk of reactivation of symptoms during treatment, and a high risk of recurrence of T1R within two months of completing the steroid regimen. Manandhar et al7 found that the levels of IFN-γ and TNF-α fell during treatment with steroids. However, the levels of TNFα increased as the steroid dose was reduced. The levels of IL-10 increased throughout the duration of treatment for T1R7. It would be worthwhile to study the utility of aforementioned markers to objectively document response to treatment.

Though the study by Sharma and colleagues in this issue8 supports these observations, unfortunately, no assay has yet been described which can predict accurately the development of T1R. TNFα and CXCR3 have shown some promise and should be researched more extensively. It would also be worth studying the utility of newer markers to further subclassify the reaction into ‘ upgrading ‘ and ‘downgrading’ reactions and to predict neural involvement and severity. This might give us better insight into the pathomechanisms of reactions in leprosy.

The use of cytokine assays is currently restricted to research, and as of today, we are relying on a thorough clinical assessment and histology if available, is still the most cost-effective, rapid and reliable way to diagnose T1R.