The difference between (steroid induced) rosacea and TSA

The two illnesses are often confused. Sometimes one is accompanied with the other. I will explain the relation here for understanding.

Rosacea is essentially the blood vessel dilation. The symptom includes pustule or burning sensation also but the main one is redness.

From the mechanism, rosacea has recently been considered as LL37 overexpression. LL37 has a strong activity of vasodilation. Why is LL37 overexpressed in rosacea? The key lies in the toll like receptor (TLR) on the epidermis. TLR exists as an old protecting system against bacteria. TLR recognizes bacteria patternally (not immunologically) and send a signal to epidermal cells. Epidermis creates natural anti-bacteria materials such as defencin-beta. This system (innate immune system) exists independently from the advanced usual immune system.

LL37 is produced by the stimuli to TLR. Rosacea is considered as the result of accelerated TLR pathway. Steroids also accelerate it and become an origin of rosacea (steroid induced rosacea).

On the other hand, the TLR pathway is also associated with the KLK5 production. KLK5 (and 7) are protease which destroy corneodesmosome. Destruction of corneodesmosome leads to thinness of epidermis, that is TSA ( Dr. Cork’s theory).


The point is that the production of LL37 is the main stream of rosacea. LL37 is always increased when the patient develops rosacea while KLK5 is not necessarily increased. So there exists steroid induced rosacea without TSA.  In such rosacea, patients can recover from the facial redness by just stopping steroids without rebound. Such steroid induced rosacea really exists.

If the patient with rosacea became TS addicted also, the patient must stand a hard rebound for withdrawal.

Moreover, there exists TSA of the face without rosacea. It is because steroids can increase protease activities and destroy corneodesmosome by the other pathway than that of TLR. Such patients develop little redness of the face. They can’t be diagnosed as rosacea. But they develop severe rebound if they try to withdraw from TS and can be diagnosed as TSA.

Recently rosacea patients due to calcineurin inhibitor have been reported. There occurs rebound phenomenon in some of such cases. The mechanism can be explained by the above figure. Calcineurin inhibitor never arises only the addiction phenomenon. It is the difference from steroids. But when it causes rosacea by putting the innate immune system (TLR pathway) out of order, the addiction (rebound) can accompany because the rosacea mechanism has an addiction mechanism in itself (KLK5).

In conclusion, the relation between the rosacea and the addiction (rebound) in TS and calcineurin inhibitor is as the following.

TS

Rosacea(－), addiction (－)	Rosacea(＋), addiction (－)
Rosacea(－), addiction (＋)	Rosacea(＋), addiction (＋)

Calcineurin inhibitor

Rosacea(－), addiction (－)	Rosacea(＋), addiction (－)
Rosacea(－), addiction (＋)　←not exists.	Rosacea(＋), addiction (＋)

References

Glucocorticoids enhance Toll-like receptor 2 expression in human keratinocytes stimulated with Propionibacterium acnes or proinflammatory cytokines.　Shibata M et al. J Invest Dermatol. 2009 Feb;129(2):375-82

Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7.Caubet C et al, J Invest Dermatol. 2004 May;122(5):1235-44

Tacrolimus-induced rosacea-like dermatitis: a clinical analysis of 16 cases associated with tacrolimus ointment application. Teraki Y et al. Dermatology. 2012;224(4):309-14

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