Page 862 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 60 Systemic Autoinflammatory Syndromes 833

A B
FIG 60.5 Renal Biopsy From a Patient With Amyloid a (AA) Amyloidosis. Amyloid deposits
are visualized by staining with Congo red (A). Under polarized light microscopy amyloid deposits
show typical apple-green birefringence (B).

an apple-green birefringence under polarized light microscopy Since the introduction of the term autoinflammation at the end
(Fig. 60.5). Progression of amyloidosis is strongly dependent of the twentieth century, the clinical characteristics of the classic
on the ability to control the underlying inflammation. If the monogenic autoinflammatory diseases FMF, CAPS, MKD, and
SAA concentration can be kept under 10 mg/L, progression of TRAPS have been described in more detail. Many new diseases
amyloidosis can be halted in many cases. Some patients even have been identified. Research focused on their pathophysiological
show regression of amyloidosis during treatment. 31-34 A cohort mechanism has revealed new genes and pathways and provided
mainly consisting of patients diagnosed with amyloidosis before further insight into the mechanism of inflammation in general.
the availability of targeted therapy showed a median survival of The development of IL-1–targeting drugs has led to better quality
19 years after the diagnosis of amyloidosis. 33 of life for patients and to increased life expectancy in some of
these diseases by prevention of complications, such as secondary
CLINICaL PEarLS amyloidosis. Nevertheless, many patients with autoinflammation
A typical case of autoinflammation remain undiagnosed.
For the near future, further study of the mechanisms of
• An 18-year-old Western European woman was seen because of inflammation in patients with autoinflammatory diseases will
recurrent episodes of fever and skin rash. These attacks started 2 likely provide a deeper insight into the workings of innate
hours after birth when a systemic maculopapular skin rash appeared. immunity and will lead to the identification of even more diseases
The rash remained present on a daily basis but was not triggered or in the autoinflammatory spectrum. The search for new therapies,
exacerbated by cold exposure.
• At the age of 2 years, the patient developed episodes of fever, preferably oral drugs, for the treatment of autoinflammation
approximately 3 days each week. Typically, she had a single daily will continue.
fever spike up to 39°C, which usually occurred in the evening. There
was no hearing loss, and arthralgia/arthritis, dysmorphia, meningitis, Please check your eBook at https://expertconsult.inkling.com/
myalgias, abdominal pain, and lymphadenopathy were also absent. for self-assessment questions. See inside cover for registration
The family history was negative for autoinflammatory diseases. details.
• On the basis of the clinical presentation, cryopyrin-associated periodic
syndrome (CAPS) was suspected as a cause, and targeted gene analysis
was performed. This showed an R260W mutation of the NLRP3 gene. REFERENCES
Thus this patient was diagnosed with CAPS.
• After the diagnosis was made, the patient was successfully treated 1. Bodar EJ, Drenth JP, van der Meer JW, et al. Dysregulation of innate
with anakinra, 100 mg once daily. When canakinumab, the long-acting immunity: hereditary periodic fever syndromes. Br J Haematol
interleukin-1 (IL-1) inhibitor, became available, she was switched to 2009;144:279–302.
150 mg canakinumab once every 2 months; she remains symptom-free.
2. van der Meer JW, Vossen JM, Radl J, et al. Hyperimmunoglobulinaemia D
and periodic fever: a new syndrome. Lancet 1984;1:1087–90.
CONCLUSIONS 3. Houten SM, van Woerden CS, Wijburg FA, et al. Carrier frequency of the
V377I (1129G>A) MVK mutation, associated with Hyper-IgD and
periodic fever syndrome, in the Netherlands. Eur J Hum Genet
ON THE HOrIZON 2003;11:196–200.
4. Simon A, Mariman EC, van der Meer JW, et al. A founder effect in the
• Identification of new (hereditary) autoinflammatory syndromes in
patients with episodic inflammation of unknown origin hyperimmunoglobulinemia D and periodic fever syndrome. Am J Med
• Wider availability and application of interleukin-1 (IL-1) inhibitors and 2003;114:148–52.
development of new IL-1 inhibitors to improve treatment. 5. Marshall GS, Edwards KM, Butler J, et al. Syndrome of periodic fever,
pharyngitis, and aphthous stomatitis. J Pediatr 1987;110:43–6.