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Postgraduate Medical Journal (November 1970) 46, 641-652.

Streptococcal skin infection and acute glomerulonephritis


Professor of Pediatrics and Associate Professor of Microbiology,University of Alabama in Birmingham, Birmingham, Alabama 35233

IntroductionThe role of streptococcal skin and soft tissue in-

fections in the development of acute glomerulo-nephritis (AGN) is now clearly established. Amongthe early studies comparing the epidemiology ofAGN and rheumatic fever it was noted that theformer complication often followed deep or sup-purative streptococcal infection, including woundinfection, whereas rheumatic fever was commonlyassociated only with superficial pharyngeal infec-tions. Impetigo, erisipelas and wound infectionswere all incriminated as antecedent infections ofAGN in early studies (Dillon, 1967). Furthermore,as recently postulated (Wannamaker, 1970), the so-called 'trench nephritis', common during WorldWar I, probably represented post-streptococcalAGN, with streptococcal skin or wound infectionbeing of primary aetiologic importance.

Interest in the role of skin infection in AGNappears to have been relatively dormant during theperiod of World War II and the immediate post-warera. In contrast, intensive interest in streptococcalpharyngeal infection was evident and it was duringthis period that the relation between streptococcalpharyngitis and acute rheumatic fever became un-equivocally established (Rammelkamp, Denny &Wannamaker, 1952). Shortly thereafter the nowclassic studies of epidemic AGN following throatinfection with streptococcal type M-12 led to theestablishment of the concept of there being 'nephri-togenic' strains of streptococci (Rammelkamp &Weaver, 1953). It soon became apparent fromstudies in widely different areas that limited serotypesof group A streptococci, notably M-types 1 and 12,accounted for most cases ofAGN following strepto-coccal sore throat (Wannamaker, 1967).

Following the observations that led to the hypo-thesis of there being nephritogenic streptococci,epidemiologic studies of impetigo in Great Britain(Parker, Tomlinson & Williams, 1955) suggestedthat limited serotypes of streptococci, most of whichwere typable at that time only by slide agglutinationserotyping (which identifies T-antigens, see below)

accounted for most cases of impetigo. These investi-gators coined the term 'impetigo streptococci'.AGN was not reported in that particular investiga-tion but it has become subsequently apparent thatthese studies represented a fundamental contributionto the understanding of differences in the epidemio-logy of streptococcal skin and pharyngeal infections.Sporadic reports of AGN following impetigo, mostof which were from the south eastern area of theUnited States where impetigo has long been recog-nized to be a perennial problem during the warmand humid months of summer and early autumn,were notable in that the streptococci isolated fromthese patients were not further identified other thanbeing beta-haemolytic organisms or group A strepto-cocci. Limitations in ability to serotype the skinstreptococci were clearly a problem in these investi-gations (Blumberg & Feldman, 1962; McCulloughet al., 1951).

In 1954, there occurred a significant epidemic ofAGN at the Red Lake Indian Reservation in northernMinnesota. Two-thirds of the sixty-three patientsreported to develop AGN were definitely consideredto have pyoderma as the antecedent of that complica-tion, with pharyngitis playing a minimal, if any, rolein the outbreak (Kleinman, 1954). The epidemicpeak ofAGN at Red Lake occurred in late summerwhen weather in that particular area is hot andhumid, not unlike that experienced in the southeastern area of the United States. The first outbreakof AGN at Red Lake is perhaps best rememberedbecause the epidemic strain of streptococcus provedto be a new serotype-M-49 (Updyke, Moore &Conroy, 1955) and was the first serotype of strepto-coccus found to be clearly related to AGN followingskin infection. This strain, subsequently known asthe Red Lake strain, has now been incriminated as acause of skin infection and AGN in many parts ofthe world.During the mid 1960s renewed interest in the role

of skin infection and AGN developed largely as aresult of extensive investigations in three particularareas: Alabama, Red Lake and Trinidad. It is

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Hugh C. Dillon

apparent that certain findings have been common toeach area. Each study has contributed distinct newinformation and collectively they have significantlyfurthered our understanding of the epidemiology ofpyoderma and AGN. The more exciting observa-tions include: the recognition of certain serotypes,including new or provisional M-types, to be ofmajor importance in AGN; further documentationof 'impetigo streptococci' as a distinct group ofstrains in which serotype and site of infectionappear clearly related; the demonstration thatstreptococcal antibody responses in skin andrespiratory infection clearly differ and some interest-ing studies of subclinical nephritis that have implica-tion with regard to the pathogenesis of AGN. Interms of numbers of cases of AGN, the Alabamastudies have revealed a consistent number of casesto occur on an endemic basis within a given popula-tion each year; limited cases of AGN occurred atRed Lake, with a second epidemic occurring in 1966and interestingly it, too, was associated with type 49streptococci (Anthony et al., 1967). In Trinidad therehave been massive epidemic waves of AGN. Type49 streptococci and at least two new serotypes havebeen incriminated in these epidemics (Parker, 1969).Some of the observations and results of studies at

Alabama are being reported in detail here. Theseresults and certain of those from Red Lake andTrinidad are compared. Individual or unique con-tributions of studies from the three particular areaswill be emphasized.

Characteristics of streptococcal impetigoStreptococcal impetigo lesions characteristically

begin as small vesicles, becoming purulent andfinally developing thickened honey-coloured crusts.A typical example of the latter type lesions is illus-trated (plate 2, between pp. 679 and 680). It is notunusual to see lesions in varying stages in a givenpatient, or among siblings within a given family. Thestreptococcal skin lesions seen among Indian childrenat Red Lake and among natives of Trinidad areremarkably similar to those illustrated here andlesions of this type clearly predominate in each area.Chronic indolent lesions ('ecthyma'), are also ob-served and collectively the various skin lesions aresimply referred to as pyoderma. The clinical appear-

ance of streptococcal impetigo is similar in patientswith and without the complication of AGN.The similarity of bacteriologic findings at Ala-

bama, Red Lake and Trinidad, have also been re-markable (Dillon, 1968; Anthony, Perlman &Wannamaker, 1967; Potter et al., 1968; Parker et al.,1968). Table 1 illustrates the frequency of recoveryof group A streptococci, with or without staphylo-cocci, from children seen during recent years inAlabama. It is to be noted that presence of staphylo-cocci in such skin lesions does not alter theirappearance. Indeed, staphylococci appear for themost part to play a secondary role. In our experiencethe presence of penicillin-resistant staphylococci inskin lesions has in no way interfered with effectivetreatment of streptococcal impetigo with penicillin(Dillon, 1970).

Limited numbers of patients with bullous impetigoare also seen in Alabama and it is in lesions of thistype that the staphylococcus is of primary aetiologicsignificance (Dillon, 1968). Most of the bullousstaphylococcal isolates are members of phage groupII, usually type 71, and may or may not be sensitiveto penicillin. When such lesions become secondarilyinfected with streptococci, as has been observed tobe the case among patients studied here, they assumethe typical purulent appearance of streptococcallesions. Infection that remains limited to staphylo-cocci leads to formation of a very thin and varnish-like crust with a bit of serous exudate at the marginof the lesion; staphylococci may be isolated fromthis margin until the lesion is healed. There are otherclinical differences observed among patients withstreptococcal impetigo as opposed to bullous im-petigo which the author has described in more detailelsewhere (Dillon, 1968). One of the principal dif-ferences, however, is the more pronounced associa-tion of lymphadenopathy with streptococcal im-petigo.

Epidemiologic features of streptococcal impetigo andacute glomerulonephritisThe peak seasonal incidence of impetigo in the

south-eastern area of the United States occurs duringthe hot and humid months of late summer and earlyautumn, and the seasonal pattern ofAGN associatedwith impetigo parallels this pattern. Fig. 2 depicts the

TABLE 1. The recovery rate for group A streptococci, with or without concomitant isolation of staphylo-cocci are shown for patients with nion-bullous impetigo seen over a period of 3 years. Patiernts with bullous

impetigo are shown for comparison

Number Total Streptococciof Group A Pure + Pure No

Clinical type patients streptococci streptococci staphylococci staphylococci growth

Non-bullous 878 92% 340 66%0 400 400Bullous 49 - - - 100%0


copyright. on 29 M

arch 2019 by guest. Protected by

Postgrad M

ed J: first published as 10.1136/pgmj.46.541.641 on 1 N

ovember 1970. D