Significance of IL36RN mutation analyses in the management of impetigo herpetiformis: A case report and review of published cases.

Impetigo herpetiformis (IH) is a rare variant of generalized pustular psoriasis (GPP), which develops during pregnancy. GPP is associated with mutations of IL36RN, but it is still unclear whether the same is true of IH. A 20-year-old Japanese woman developed erythema and pustules on her trunk during the 27th week of her first pregnancy. Within 1 month, the skin lesions spread over her whole body, accompanied by fever. Skin biopsy revealed Kogoj's spongiform pustules in the epidermis and she was diagnosed with IH. Systemic administration of prednisolone failed to resolve the skin eruption, but it was partially improved by the addition of cyclosporin. The patient gave birth to a healthy female infant. After delivery, her erythema relapsed and the effect of granulocyte and monocyte adsorption apheresis was limited. Thus, secukinumab was administrated, and since then, she has maintained complete remission. Mutation analysis revealed a homozygous c.28C>T (p.Arg10X) mutation in IL36RN. Twelve cases of IH, including that presented here, have been reported together with the results of IL36RN genetic analyses, and 10 of the 12 cases occurred in East Asia (Japan and China) despite the fact that IL36RN mutations in GPP have been reported worldwide. Among 10 IH patients of East Asian descent, seven had IL36RN mutations, all of which were founder mutations causing GPP in East Asia: c.28C>T (p.Arg10X) or c.115+6T>C (p.Arg10ArgfsX1). Thus, East Asian founder mutations may play an important role in the pathogenesis of IH. IH patients with IL36RN mutations have a tendency to require biologics to resolve postpartum flare-ups or sustained psoriatic skin lesions. Because IL36RN mutation status may help predict postpartum flare-ups in IH patients, mutation analysis should be considered to enable preparation for biologic therapy of intractable flare-ups.

Clinical course in a patient with neutrophil-specific granule deficiency and rapid detection of neutrophil granules as a screening test.

PURPOSE: Neutrophil-specific granule deficiency (SGD) is a rare, congenital disorder characterized by atypical neutrophil structure and function that results in frequent and severe bacterial infections. However, the clinical course of patients with SGD have not been described in detail because of the scarcity of the disease. We present the clinical course of an adult patient with SGD and propose a method for making an early diagnosis of SGD. PATIENT AND METHODS: A32-year-old Japanese woman with SGD had a small impetigo lesion on her face and experienced the rapid spread of a facial abscess to a pulmonary abscess via the blood stream. We also analyzed the expression of neutrophil granule proteins in our patient compared with a healthy control by flow cytometry. RESULTS: We confirmed defects of several neutrophil granule proteins in our patient by flow cytometry. CONCLUSION: Severe bacterial infections sometimes occur and spread rapidly in SGD. Detection of neutrophil granules by flow cytometry is useful for a rapid diagnosis and a screening of SGD.

Dissemination of multiple MRSA clones among community-associated methicillin-resistant Staphylococcus aureus infections from Japanese children with impetigo.

The proportion of MRSA strains that cause skin and soft infections has recently increased. In 3 months we have characterized 17 MRSA strains isolated from children with impetigo at a Japanese hospital. Seventeen MRSA strains belonged to 7 clones defined by clonal complex (CC) in MLST genotype and type of SCCmec, which were rarely identified among healthcare-associated MRSA: CC 91-SCCmecIIb (4 strains); CC91-SCCmecIIn (2 strains); CC91-SCCmecIVa (2 strains); CC91-SCCmecV (4 strains); CC88-SCCmecIVg (3 strains); CC1-SCCmecIVc (1 strain); and CC5-SCCmecIVn (1 strain). Although one strain belonged to CC5, which has been commonly identified in healthcare-associated MRSA, it did not carry type II SCCmec, but carried type IV SCCmec. Fourteen of the 17 strains carried exfoliative toxin a or b gene, and none carried Panton-Valentine leukocidine gene. Furthermore, we determined the entire nucleotide sequences of two type V SCCmec elements carried by strains JCSC5952, a CC91 strain, and TSGH17, a Taiwanese CC59 strain. The structure of SCCmecJCSC5952 was more than 99% homologous in nucleotide identity with those of Taiwanese PVL-positive ST59 MRSA strains TSGH17 and PM1, which were designated as type V (5C2&5). Identification of multiple MRSA clones distinct from those disseminating at the hospital suggests that MRSA strains might be emerging in the community from MSSA strains by acquiring SCCmec elements on various occasions. Carriage of the similar type V(5C2&5) SCCmec element by strains of distinct genetic backgrounds, CC91 and CC59, suggested horizontal transfer of the SCCmec element.

A fusidic acid-resistant clone of Staphylococcus aureus associated with impetigo bullosa is spreading in Norway.

OBJECTIVE: To investigate the possibility that the increased prevalence of fusidic acid-resistant Staphylococcus aureus in Norway is caused by clonal spread. METHODS: Fusidic acid-resistant and -susceptible clinical isolates of S. aureus from patients with skin infections in the Norwegian county of Telemark and fusidic acid-resistant isolates from other parts of Scandinavia were compared. MICs of fusidic acid for bacterial isolates and pulsed-field gel electrophoresis (PFGE) patterns were investigated. Prevalence data for fusidic acid-resistant S. aureus for the period 1992-2001 were obtained. RESULTS: The prevalence of fusidic acid resistance in S. aureus increased from 1992 to 2001. Eighty per cent of the resistant isolates investigated shared an identical PFGE pattern. The same pattern was found in fusidic acid-resistant isolates from other parts of Scandinavia. Fusidic acid-resistant S. aureus was typically found in impetigo bullosa-like skin disease in children mostly in the summer months. CONCLUSIONS: Fusidic acid resistance among S. aureus is increasing in Norway and is predominantly caused by one clone of S. aureus. The clone may spread further to other countries, and dissemination may be facilitated by extensive use of topical fusidic acid.

Familial juvenile generalized pustular psoriasis.

The acral form of generalized pustular psoriasis is characterized by macroscopic pustules surmounting erythematous plaques that may progress from a localized distal eruption to involve the entire cutaneous surface. Juvenile-onset and familial-generalized pustular psoriasis are rare; familial-juvenile-generalized pustular psoriasis is exceptionally uncommon. A kindred of three children in the same generation had chronic, localized-acral pustular psoriasis and episodic-generalized pustular psoriasis.

Natural history of impetigo. I. Site sequence of acquisition and familial patterns of spread of cutaneous streptococci.

The appearance on and spread of Group A streptococci among different body sites in relationship to the development of impetigo were studied prospectively in 31 children in five families. During July and August 1969 intensive clinical, bacteriological, and serological observations were made, including cultures taken at least every other day. In individual children, site sequence of spread of Group A streptococci was from normal skin to lesions and finally to respiratory tract. Streptococci were recovered from normal skin before development of lesions (mean interval of 10 days) in 74% of episodes. Recovery of streptococci from nose and throat followed (by means of 14 and 20 days, respectively) skin acquisition of streptococci (97% of episodes) and lesions (74% of episodes).Distribution of positive normal skin sites among wrist, ankle, and back was similar (28-37%) although 62% of lesions were on the legs. Recovery of a serotype from normal skin was associated with a high risk (76%) of subsequent development of lesions due to that type. New streptococcal serotypes usually entered a family during the peak or decline of a preceding serotoype with a tendency of one to predominate. Among family members the mean interval from index to secondary skin acquisition of streptococci was 4.8 days, but 21 days elapsed from first appearance to last acquisition of skin disease. In the population as a whole, streptococci were recovered in high frequency from normal skin before the increase in prevalence of lesions and also later in the fall when cutaneous infections were absent.

Natural history of impetigo. II. Etiologic agents and bacterial interactions.

Intensive observations on 37 children in a population with endemic skin infections provided an opportunity to study the interrelationships between and the significance of the bacterial genera commonly associated with impetigo. Cultures of the respiratory tract, three normal skin sites, and lesions, when present, were taken three times weekly from July to October 1969. Impetigo developed in all 37 children. Group A streptococci alone were recovered from 21% of 361 lesions, Staphylococcus aureus alone from 8%, Staphylococcus epidermidis alone from 5% and mixtures of streptococci and staphylococci from 61%. Vesicular or pustular lesions were more often pure streptococcal than pure staphylococcal. Streptococci alone were more often recovered from early stage lesions rather than from later ones. The pure staphylococcal lesions characteristically occurred early in the season whereas streptococcal or mixed lesions had later peaks.Serial observations on 74 lesions revealed longer persistence of streptococci than staphylococci in mixed lesions. In 85% of the instances the same streptococcal serotype was recovered repeatedly from an individual lesion, whereas staphylococcal types changed in 57% of instances. Phage type 75 accounted for the majority of staphylococcal isolates from all sites, whereas phage type 54 was recovered only from skin lesions. In contrast to streptococci, the site sequence of staphylococcal spread was from the nose to normal skin to skin lesions. These studies reveal important differences in the migration of staphylococci (as compared with streptococci) to various body sites and suggest a subsidiary role for staphylococci in nonbullous impetiginous lesions yielding both organisms.