Identification of a Homozygous PSTPIP1 Mutation in a Patient With a PAPA-Like Syndrome Responding to Canakinumab Treatment

Figure 1. Patient at the time when the pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA)–like syndrome was diagnosed. A and B, Shown are acne fulminans on the back (A) and pyoderma gangrenosum on the left upper leg (B) of the patient. Note the atrophic scar on the left lower leg. C, The pedigree of the patient (solid square) is shown; dots within circles (female relatives) or squares (male relatives) indicate heterozygous asymptomatic carriers of the p.Gly258Ala mutation. The patient carries a homozygous mutation. As expected, both parents carry a mutant allele, which they inherited from their mothers, who are sisters (both heterozygous for p.Gly258Ala). All the remaining heterozygous individuals are siblings of the patient's mother. Results from the sequencing analysis of PSTPIP1 and from the c.773G>C genotyping for the patient, his siblings, and his parents are shown. co indicates control; het, heterozygous individual; hom, individual carrying the mutant variant homozygously; and wt, individual carrying the wild-type variant. D, Erythematous painful patches are seen at the application site of anakinra, a recombinant human interleukin 1 receptor antagonist.

Figure 2. Patient after cessation of systemic corticosteroids. A, Before treatment with canakinumab, the patient had dense folliculitis in the neck and face area. B, During treatment with canakinumab, complete remission is seen at the same sites after 9 months and 3 injections of canakinumab. C, Response patterns to canakinumab injections (150 mg subcutaneously) in the C-reactive protein (CRP) and serum amyloid A (SAA) levels are shown in the patient over time. The arrows indicate the canakinumab injections every 8 weeks (at days 57, 110, 167, and 223). At day 0 (6 days before the first injection of canakinumab), the CRP and SAA levels increased significantly. Note that the normal levels of CRP and SAA are less than 1 mg/dL and 0 to 6.4 mg/L, respectively (to convert C-reactive protein level to nanomoles per liter, multiply by 9.524). Within a few days after the first injection, the CRP and SAA levels dropped, accompanied by significant clinical improvement. Subsequently, the curves seem to follow a decrescendo pattern associated with the injections.