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other non-infectious danger signals. Uncontrolled NSPs are involved in neutrophil-mediated inflammatory
diseases and are considered as important therapeutic targets. CatC attracts more and more attention from
both scientists and clinicians because of its role in the activation of pro-inflammatory NSPs implicated in
certain chronic inflammatory/auto-immune disorders. Promising preclinical and clinical data suggest that
pharmacological inhibition of NSPs might ameliorate these conditions.

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive trait caused by mutations in the CTSC gene
which encodes CatC . Patients with PLS have a genetically determined deficiency in CatC but,
[1-3]
reassuringly, do not exhibit marked immunodeficiency despite the absence of NSPs in immune defense
cells. Hence, the pharmacological control of CatC activity in bone marrow precursor cells represents an
attractive therapeutic strategy for neutrophil serine protease-mediated disorders. A variety of CatC
inhibitors, developed by pharmaceutical companies and academic investigators, are currently being
evaluated in preclinical/clinical trials as anti-inflammatory drugs. An invited review article on the
therapeutic targeting of CatC resulted from the first International Symposium on Cathepsin C IsyCatC
(Tours/France, April 2017) and was published in the journal Pharmacology and Therapeutics .
[3]
A CatC inhibitor is currently being tested in Phase 3 in patients with bronchiectasis, a chronic inflammatory
lung disease defined by permanent dilatation of the bronchi. This development is very encouraging for
biochemists studying the functionality of CatC, cell biologists studying its maturation and tissue
localization, chemists developing specific CatC inhibitors and clinicians managing patients with NSPs-
mediated disorders. Due to overlapping phenotypes and similar underpinning molecular mechanisms for
several inflammatory diseases, a positive effect in bronchiectasis could be translated directly to the potential
treatment of other NSPs-mediated inflammatory diseases. It is gratifying to see that the hard work of all
colleagues from academic labs and industry and advocacy in the CatC field may have a clinical payoff.

In 1924, two French physicians, Paul Henri Papillon (1866-1945) and Paul Philippe Henri Lefèvre (1891-
1982), working at the Armand Trousseau Children’s Hospital in Paris, observed severe lesions on the palms
and soles of two siblings with extensive dental decay. The coexistence of palmoplantar keratoderma with
dental decay was novel and highlighted in the article they published on February 14, 1924, in French, in Bull
[4]
Soc Fr Dermatol Syph, 1924;31:82-7 [Figure 1]. The disease characterized by these symptoms was named
“Papillon-Lefèvre syndrome” (PLS) after the 1960s and is characterized by severe periodontitis and
palmoplantar keratoderma developing between the first and fifth years of life, with subsequent loss of
teeth . We present in this Editorial the initial article describing the first patients with biographical
[1,2]
information about Dr. Papillon and Dr. Lefèvre, including unpublished pictures from the archives.

Paul Henri Papillon, son of Louis Alexandre Papillon and Pauline Suzanne Papillon, was born in Paris, in
the city’s 1st arrondissement, on January 4, 1866. His father was a grocer and his mother was a housewife. In
1896, he married Marguerite Coulbaux (1873-1906), with whom he had a son, Jacques Papillon (1899-1984).
Paul Henri Papillon graduated from the Paris School of Medicine and completed internships between 1889
and 1892. His thesis for the doctorate in medicine entitled « Study of histological lesions of the liver and
kidneys in cholera (Beaujon epidemic 1892) » was published in 1893. He was a paediatrician and was
appointed head of department at Sainte Périne Hospital, Paris on February 1, 1911 [Figure 2]. He worked as
head of Auxiliary Hospital 31 at Levallois Perret during the 1st world war, where his service earned him in
1921 the highest French honour for military and civil merit awarded by the French Ministry of War, Knight
of the Legion of Honour for his professionalism as a physician during the world war [Figure 3]. He
completed 14 years of service as a physician in Paris Hospitals [Figures 4 and 5]. He was appointed head of
the infectious disease department in Armand Trousseau Children’s Hospital in Paris on February 1, 1921,