Editing Group A streptococcal infection (section)

== Complications ==<!-- [[Rapid Strep Test]] links to here -->

* [[Post-streptococcal glomerulonephritis]]
* [[PANDAS|Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)]]
* [[Rheumatic fever]]
* [[Scarlet fever]] 
* [[Toxic shock syndrome]]

===Acute rheumatic fever===
[[Acute rheumatic fever]] (ARF) is a complication of respiratory infections caused by GAS. The M-protein generates antibodies that cross-react with autoantigens on interstitial connective tissue, in particular of the endocardium and synovium, that can lead to significant clinical illness.

Although common in developing countries, ARF is rare in the United States, possibly secondary to improved antibiotic treatment, with small isolated outbreaks reported only occasionally. It is most common among children between 5 and 15 years old and occurs 1–3 weeks after an untreated GAS pharyngitis, but caution is advised when interpreting the demographics of the contemporary picture of pediatric cases in the United States.<ref name="pmid34348475">{{cite journal | vauthors = de Loizaga SR, Arthur L, Arya B, Beckman B, Belay W, Brokamp C, Hyun Choi N, Connolly S, Dasgupta S, Dibert T, Dryer MM, Gokanapudy Hahn LR, Greene EA, Kernizan D, Khalid O, Klein J, Kobayashi R, Lahiri S, Lorenzoni RP, Otero Luna A, Marshall J, Millette T, Moore L, Muhamed B, Murali M, Parikh K, Sanyahumbi A, Shakti D, Stein E, Shah S, Wilkins H, Windom M, Wirth S, Zimmerman M, Beck AF, Ollberding N, Sable C, Beaton A | title = Rheumatic Heart Disease in the United States: Forgotten But Not Gone: Results of a 10 Year Multicenter Review | journal = J Am Heart Assoc | volume = 10 | issue = 16 | pages = e020992 | date = August 2021 | pmid = 34348475 | pmc = 8475057 | doi = 10.1161/JAHA.120.020992 }}</ref>

ARF is often clinically diagnosed based on [[Acute rheumatic fever#Diagnosis|Jones Criteria]], which include: [[pancarditis]], migratory [[polyarthritis]] of large joints, [[Subcutaneous tissue|subcutaneous]] nodules, [[erythema marginatum]], and [[sydenham chorea]] (involuntary, purposeless movement). The most common clinical finding is a migratory arthritis involving multiple joints.<ref>{{Cite book |last1=Sika-Paotonu |first1=D. |title=Streptococcus pyogenes : Basic Biology to Clinical Manifestations |last2=Beaton |first2=A. |last3=Raghu |first3=A. |last4=Steer |first4=A. |last5=Carapetis |first5=J. |publisher=University of Oklahoma Health Sciences Center |year=2016 |location=Oklahoma City |chapter=Acute Rheumatic Fever and Rheumatic Heart Disease |pmid=28379675 |author-link=Dianne Sika-Paotonu |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK425394/}}</ref>

Other indicators of GAS infection such as a [[DNAase]] or [[antistreptolysin|ASO]] serology test must confirm the GAS infection. Other minor Jones Criteria are fever, elevated [[erythrocyte sedimentation rate|ESR]] and [[arthralgia]]. One of the most serious complications is pancarditis, or inflammation of all three heart tissues. A fibrinous [[pericarditis]] can develop with a classic friction rub that can be auscultated. This will give increasing pain upon reclining.

Further endocarditis can develop with aseptic vegetations along the valve closure lines, in particular the mitral valve. Chronic rheumatic heart disease mostly affects the [[mitral valve]], which can become thickened with calcification of the leaflets, often causing fusion of the commissures and [[chordae tendineae]].

Other findings of ARF include [[erythema marginatum]] (usually over the spine or other bony areas) and a red expanding rash on the trunk and extremities that recurs over weeks to months. Because of the different ways ARF presents itself, the disease may be difficult to diagnose.

A neurological disorder, Sydenham [[Chorea (disease)|chorea]], can occur months after an initial attack, causing jerky involuntary movements, muscle weakness, slurred speech, and personality changes. Initial episodes of ARF, as well as recurrences, can be prevented by treatment with appropriate antibiotics.

It is important to distinguish ARF from [[rheumatic heart disease]]. ARF is an acute inflammatory reaction with pathognomonic [[Aschoff body|Aschoff bodies]] histologically and RHD is a non-inflammatory sequela of ARF.

===Post-streptococcal glomerulonephritis===
[[Post-streptococcal glomerulonephritis]] (PSGN) is an uncommon complication of either a strep throat or a streptococcal skin infection. It is classified as a type III hypersensitivity reaction. Symptoms of PSGN develop within 10 days following a strep throat or 3 weeks following a GAS skin infection. PSGN involves inflammation of the kidney.  Symptoms include pale skin, lethargy, loss of appetite, headache, and dull back pain. Clinical findings may include dark-colored urine, swelling of different parts of the body (edema), and high blood pressure. Treatment of PSGN consists of supportive care.

===PANDAS===
[[Obsessive–compulsive disorder]] and [[tic disorder]]s are hypothesized to arise in a subset of children as a result of a post-[[streptococcus|streptococcal]] autoimmune process.<ref name= Dale2017/><ref name= Marazziti2018/><ref name= Zibordi2018/> Its potential effect was described in 1998 by the controversial hypothesis called [[PANDAS]] (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), a condition thought to be triggered by GABHS infections.<ref name= Wilbur2019>{{cite journal |vauthors=Wilbur C, Bitnun A, Kronenberg S, Laxer RM, Levy DM, Logan WJ, Shouldice M, Yeh EA |title=PANDAS/PANS in childhood: Controversies and evidence |journal=Paediatr Child Health |volume=24 |issue=2 |pages=85–91 |date=May 2019 |pmid=30996598 |pmc=6462125 |doi=10.1093/pch/pxy145}}</ref><ref name=Sigra2018>{{cite journal |vauthors=Sigra S, Hesselmark E, Bejerot S |title=Treatment of PANDAS and PANS: a systematic review |journal=Neurosci Biobehav Rev |volume=86 |issue= |pages=51–65 |date=March 2018 |pmid=29309797 |doi=10.1016/j.neubiorev.2018.01.001 |s2cid=40827012 |doi-access=free }}</ref> The PANDAS hypothesis is unconfirmed and unsupported by data, and two new categories have been proposed: [[PANDAS|PANS]] (pediatric acute-onset neuropsychiatric syndrome) and CANS (childhood acute neuropsychiatric syndrome).<ref name= Marazziti2018/><ref name= Zibordi2018/> The CANS/PANS hypotheses include different possible mechanisms underlying acute-onset neuropsychiatric conditions, but do not exclude GABHS infections as a cause in a subset of individuals.<ref name= Marazziti2018/><ref name= Zibordi2018/> PANDAS, PANS and CANS are the focus of clinical and laboratory research but remain unproven.<ref name= Dale2017>{{cite journal |vauthors=Dale RC |title=Tics and Tourette: a clinical, pathophysiological and etiological review |journal=Curr Opin Pediatr |volume=29 |issue=6 |pages=665–673 |date=December 2017 |pmid=28915150 |doi=10.1097/MOP.0000000000000546 |s2cid=13654194 |type= Review}}</ref><ref name= Marazziti2018>{{cite journal |vauthors=Marazziti D, Mucci F, Fontenelle LF |title=Immune system and obsessive-compulsive disorder |journal=Psychoneuroendocrinology |volume=93 |pages=39–44 |date=July 2018 |pmid=29689421 |doi=10.1016/j.psyneuen.2018.04.013 |s2cid=13681480 |type= Review}}</ref><ref name= Zibordi2018>{{cite journal |vauthors=Zibordi F, Zorzi G, Carecchio M, Nardocci N |title=CANS: Childhood acute neuropsychiatric syndromes |journal=Eur J Paediatr Neurol |volume=22 |issue=2 |pages=316–320 |date=March 2018 |pmid=29398245 |doi=10.1016/j.ejpn.2018.01.011 |type= Review}}</ref>