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Staphylococcal Ophthalmia Neonatorum and the Staphylococcal Scalded Skin Syndrome
STAPHYLOCOCCAL OPHTHALMIA NEONATORUM AND T H E STAPHYLOCOCCAL SCALDED SKIN SYNDROME K E N N E T H R. F O X , M.D.,
AND H E R B E R T S. G O L O M B ,
Washington,
Ophthalmia neonatorum 1 is usually a mild, catarrhal, blepharoconjunctivitis. Staphylococcal organisms are a frequent cause of ophthalmia neonatorum, and oc casionally they may cause serious ocular complications, involving the cornea, the globe itself, or the ocular adnexal struc tures. Another complication, however, of staphylococcal ophthalmia neonatorum is the staphylococcal scalded skin syn drome. 2 , 3 This syndrome is a generalized exfoliative dermatitis that frequently in volves neonates, and results from an ini tial focal staphylococcal infection. Be cause staphylococcal ophthalmia neona torum may predispose to staphylococcal scalded skin syndrome, all ophthalmolo gists and pediatricians should be aware of this complication. We describe herein a case of staphylococcal ophthalmia neona torum that rapidly developed into staphy lococcal scalded skin syndrome. CASE REPORT On July 9, 1978, a 3-week-old baby girl was noted by her parents to have developed a pus-like dis charge from her left eye which clinically resembled a mild blepharoconjunctivitis. The infant was seen by her pediatrician on July 11, 1978, and was treated for ophthalmia neonatorum with polymyxin B, neomycin and hydrocortisone (Cortisporin) ophthalmic solution to both eyes, four times a day. By July 13, the infection had spread. Clinically the eyes were noted to be more inflamed, the eyelids were edematous, and the perioral region had become involved with an erythematous eruption. At this time fluocinolone acetonide (Synalar cream) was added for management of the perioral skin lesions. By July 15, the trunk and legs had become involved with an erythematous rash, involving scaling of the skin. From the Metropolitan Retina-Vitreous Founda tion (Dr. Fox), Washington, D . C ; and the Depart ment of Dermatology (Dr. Golomb), the George Washington University School of Medicine, Wash ington, D.C. Reprint requests to Kenneth R. Fox, M.D., 6060 Arlington Blvd., Falls Church, VA 22044. 1052
M.D.
D.C.
The inflammations around the eyes and around the mouth persisted. The patient was referred for emer gency admission to a local hospital. The patient's medical history was noncontributory. She was the product of a full-term, uncomplicat ed pregnancy and a normal delivery. There were no known allergies, and the patient received no system ic medications. No family members or any other contacts were known to have illnesses during this perinatal period. After admission on July 15, the patient was placed in the intensive care nursery and was ob served by the infectious disease service of the hospi tal, with consultations by the ophthalmic and otorhinolaryngologic services. At no time during the hospitalization was a dermatology consultation re quested, nor was a skin biopsy performed. The infectious disease service suggested the diagnosis of toxic epidermal necrolysis. 4 The patient was given a course of oxacillin, 116 mg, intravenously four times a day, until July 20 (for a total of five days). The treatment was then changed to dicloxacillin, 62.5 mg orally three times a day, for five additional days, at which time all the antibiotics were discontinued. During the hospitalization cultures were taken of the discharge from the left eye, the skin of the face, and the left ear. All cultures were positive for Staphylococcus aureus, and all were sensitive to all antibiotics tested. The patient's skin throughout the body, including the trunk, the two lower extremities, and the periorbital and perioral regions, improved gradually over the six days before discharge on July 21. After dis charge, total clearing of the skin lesions occurred over the course of the next two weeks. No systemic signs throughout the entire period were noted and after resolution of the skin lesions, there has been no recurrence. DISCUSSION
Ophthalmia neonatorum is a common and well recognized clinical entity. It is frequently seen by pediatricians in the perinatal period, and it is well known to ophthalmologists. Although S. aureus is the most frequent cause for ophthalmia neonatorum, there are many other causal organisms. Staphylococcus aureus is common in the neonates' environment and may readily appear in the conjunctival sac. For many reasons it may easily become the source of the blepharo conjunctivitis of ophthalmia neonatorum.
AMERICAN JOURNAL O F OPHTHALMOLOGY 88:1052-1055, 1979
VOL. 88, NO. 6
STAPHYLOCOCCAL OPHTHALMIA NEONATRUM
The neonate produces little if any tears, has not had the opportunity to develop immunity to staphylococcal organisms, and does not benefit from the presence of lymphoid tissue in the periorbital area for protection against these organisms. Many phage types exist for S. aureus, and the production of exotoxin by the bacteria enhances its rapid infectious activity. Staphylococcal organisms are nearly ubiquitous and the neonate has an oppor tunity to come in contact with the germ by contact with the mother, other human contacts in the perinatal period, nursery environment, or at home. The lower nares may become infected and the organisms will appear on the lower eyelid and sub sequently in the conjunctiva. The time of onset of staphylococcal ophthalmia neonatorum can be any time after birth. The infection is usually rela tively mild and represents a subacute catarrhal blepharoconjunctivitis with mild discharge and conjunctival injec tion. The infection may at times become more purulent with conjunctival chemosis and eyelid edema. Ocular complica tions occasionally involve the following: staphylococcal corneal ulcers that may perforate, corneal infiltrates, hypopyon with iridocyclitis, endophthalmitis, bac terial venous thrombosis, purulent sinusi tis, empyema, pneumonia, osteomyelitis, deep abscess formation, or staphylococcal metastatic spread. The staphylococcal scalded skin syn drome is a generalized exfoliative derma titis of infants and children, associated with an infection with staphylococcal or ganisms of the phage Group 2. This syn drome was formerly known as Ritter's disease and toxic epidermal necrolysis of Lyell. This disease in its most severe form is characterized by the sudden onset of widespread reddening and tenderness of the skin followed by the exfoliation of large areas of skin so that they appear rumpled, like wet wallpaper. As the skin
1053
peels off, a dark red, painful, glistening surface is exposed. This clinical appear ance resembles the scalding caused by a burn. These changes of staphylococcal scald ed skin syndrome are the result of an infection caused by an epidermal toxin produced by the dermopathic strains of the 5. aureus bacteria. These are often, but not always, members of the phage Group 2 (Types 3A, 3B, 3C, 55, and 71). These staphylococci may be isolated from both the involved skin and the areas of the body remote to the skin eruptions. The toxin cleaves the epidermis beneath the stratum granulosum. Eruption is sometimes preceded by a relatively in nocuous staphylococcal ophthalmia neo natorum that may insidiously develop into a purulent blepharoconjunctivitis. Certain other predisposing staphylococ cal focal infections, including those of the external nares, may predispose to the de velopment of staphylococcal scalded skin syndrome as well. The cutaneous course begins with tenderness and a distinctive faint, macular, yellow orange or brick red eruption. This is characteristically dis tributed in the central portion of the face, on the neck, in the axillae, and in the groin. There is often a positive Nikolsky's sign at this time. This scarlatina-form eruption within 24 to 48 hours usually progresses to spontaneous wrinkling and large flaccid bullae characteristic of the appearance of staphylococcal scalded skin syndrome. The upper part of the epidermis separates in sheets and ribbons and the moist, erythematous base is seen. This dries quickly and recovery usually takes place within seven days, especially if antibiotic therapy is given early in the course of the disease. Localized forms of staphylococcal scalded skin syndrome occur and may be dependent upon a variety of host factors. There is an association between the infec tion with Phage Group 2 staphylococci
1054
AMERICAN JOURNAL OF OPHTHALMOLOGY
and localized bullous impetigo. There are also several reports of a scarlatina-form eruption that is also the result of an infec tion with this organism. This eruption is an abortive form that does not advance to the full exfoliative stage. The histologic examination is pathognomonic for diag nosis of staphylococcal scalded skin syn drome. This can be accomplished rapidly by examination of a frozen section of involved skin or by performing the Tzank test on involved skin areas. The larger clinical entity of "scalded skin syndrome" does have a differential diagnosis worth noting. The epidemi ology of this case, however, is typical only for staphylococcal scalded skin syn drome, and the clinical appearance is classic for that specific cause, the most common in neonates. Moreover, numer ous positive 5. aureus cultures were grown out. Bullous erythema multiforme, Leiner's disease, and bullous congenital ichthyosiform erythroderma are the much more unusual causes of infant scalded skin syndromes. Bullous erythema multiforme is rare in infants, but is caused by drug reactions, and is frequently seen in adults. This group of drugs includes anti biotics, including primarily penicillin, and, occasionally, sulfonamides, but never polymyxin B sulfate (Neosporin). Others include antipyretics, antimalarials, barbiturates, mercury, arsenic, phenylbutazone, hydantoins and phenophthalein. Our patient was not exposed to any of these. In our case, Leiner's disease was ruled out by the clinical lack of heavy scaling, a typical sign of that disease of the infant. Bullous congenital ichthyosiform eryth roderma, which is hereditary, was ruled out by a lack of evidence of familial involvement, and the short-lived course of the treated entity in our patient. That disease runs a chronic course invariably. Appropriate antibiotic management for
DECEMBER, 1979
S. aureus blepharoconjunctivitis of oph thalmia neonatorum involves appropriate early microbiologic studies including at least Gram staining and culture. Topical antibiotics are normally effective and there is no specific role for topical corticosteroids. Antibiotic sensitivities are im portant because of the frequent penicillin resistance of 5. aureus. In cases of infec tion with the more virulent strains of 5. aureus, and particularly those that are penicillin resistant, a more serious local ized blepharoconjunctivitis may develop with local sequelae, and a more rapid development of staphylococcal scalded skin syndrome may ensue. Oral or parenteral antibiotics, and in the neonatal peri od, hospitalization for more intensive management, may be indicated in these cases. Although the general prognosis for resolution of the ocular sequelae of staph ylococcal blepharoconjunctivitis, and the dermatologic sequelae of staphylococ cal scalded skin syndrome are relatively good, early diagnosis and prompt man agement are imperative. Because of the virulence of some S. aureus organisms, the variable host defenses including a lack of immunity, the variety of serious sequelae that staphylococcal infections may cause, and the lack of predictability as to the identification of which staphylo coccal infections may become particular ly virulent, casual management of possi ble staphylococcal ophthalmia neonato rum cannot be recommended. An awareness of the possible ophthalmic-dermatologic consequences of ne onatal staphylococcal infection, which initially appears as a mild catarrhal oph thalmia neonatorum of a nonspecific na ture, is imperative. Consequently, early bacteriologic evaluation should be made in all patients. Prompt management with topical antibacterial agents, and without the concurrent use of possibly exacerbat ing topical anti-inflammatory agents, is indicated. This management regimen
VOL. 88, NO. 6
STAPHYLOCOCCAL OPHTHALMIA NEONATRUM
1055
should yield rapid satisfactory resolution in most cases. Attention to the skin and recognition of the early dermatologic signs of staphylococcal scalded skin syn drome should be a part of the manage ment of ophthalmia neonatorum.
and the understanding that it may rapidly become a serious consequence of staphy lococcal ophthalmia neonatorum. We stress the need for initial microbiologic studies and early antibiotic therapy for ophthalmia neonatorum.
SUMMARY
REFERENCES
A 3-week-old infant had neonatal oph thalmia neonatorum, treated in a routine manner which rapidly developed into an advanced case of staphylococcal scalded skin syndrome. The infant had sudden onset of widespread erythematous and tender areas of skin with subsequent ex foliation of large surface areas. We em phasize the recognition of this syndrome
1. Duke-Elder, S.: Diseases of the Outer Eye. Conjunctiva. In System of Ophthalmology, vol. 8, pt. 1. London, Henry Kimpton, 1965, p p . 115-119; 154-158. 2. Melish, M. E.: The staphylococcal scalded skin syndrome. N. Engl. J. Med. 282:1114, 1970. 3. Elias, P. M., Fritsch, P., and Epstein, E. H.: Staphylococcal scalded skin syndrome. Arch. Dermatol. 113:207, 1977. 4. Lyell, A.: Toxic epidermal necrolysis. The scalded skin syndrome. J. Cont. Ed. Dermatol. 1:15, 1978.
AND H E R B E R T S. G O L O M B ,
Washington,
Ophthalmia neonatorum 1 is usually a mild, catarrhal, blepharoconjunctivitis. Staphylococcal organisms are a frequent cause of ophthalmia neonatorum, and oc casionally they may cause serious ocular complications, involving the cornea, the globe itself, or the ocular adnexal struc tures. Another complication, however, of staphylococcal ophthalmia neonatorum is the staphylococcal scalded skin syn drome. 2 , 3 This syndrome is a generalized exfoliative dermatitis that frequently in volves neonates, and results from an ini tial focal staphylococcal infection. Be cause staphylococcal ophthalmia neona torum may predispose to staphylococcal scalded skin syndrome, all ophthalmolo gists and pediatricians should be aware of this complication. We describe herein a case of staphylococcal ophthalmia neona torum that rapidly developed into staphy lococcal scalded skin syndrome. CASE REPORT On July 9, 1978, a 3-week-old baby girl was noted by her parents to have developed a pus-like dis charge from her left eye which clinically resembled a mild blepharoconjunctivitis. The infant was seen by her pediatrician on July 11, 1978, and was treated for ophthalmia neonatorum with polymyxin B, neomycin and hydrocortisone (Cortisporin) ophthalmic solution to both eyes, four times a day. By July 13, the infection had spread. Clinically the eyes were noted to be more inflamed, the eyelids were edematous, and the perioral region had become involved with an erythematous eruption. At this time fluocinolone acetonide (Synalar cream) was added for management of the perioral skin lesions. By July 15, the trunk and legs had become involved with an erythematous rash, involving scaling of the skin. From the Metropolitan Retina-Vitreous Founda tion (Dr. Fox), Washington, D . C ; and the Depart ment of Dermatology (Dr. Golomb), the George Washington University School of Medicine, Wash ington, D.C. Reprint requests to Kenneth R. Fox, M.D., 6060 Arlington Blvd., Falls Church, VA 22044. 1052
M.D.
D.C.
The inflammations around the eyes and around the mouth persisted. The patient was referred for emer gency admission to a local hospital. The patient's medical history was noncontributory. She was the product of a full-term, uncomplicat ed pregnancy and a normal delivery. There were no known allergies, and the patient received no system ic medications. No family members or any other contacts were known to have illnesses during this perinatal period. After admission on July 15, the patient was placed in the intensive care nursery and was ob served by the infectious disease service of the hospi tal, with consultations by the ophthalmic and otorhinolaryngologic services. At no time during the hospitalization was a dermatology consultation re quested, nor was a skin biopsy performed. The infectious disease service suggested the diagnosis of toxic epidermal necrolysis. 4 The patient was given a course of oxacillin, 116 mg, intravenously four times a day, until July 20 (for a total of five days). The treatment was then changed to dicloxacillin, 62.5 mg orally three times a day, for five additional days, at which time all the antibiotics were discontinued. During the hospitalization cultures were taken of the discharge from the left eye, the skin of the face, and the left ear. All cultures were positive for Staphylococcus aureus, and all were sensitive to all antibiotics tested. The patient's skin throughout the body, including the trunk, the two lower extremities, and the periorbital and perioral regions, improved gradually over the six days before discharge on July 21. After dis charge, total clearing of the skin lesions occurred over the course of the next two weeks. No systemic signs throughout the entire period were noted and after resolution of the skin lesions, there has been no recurrence. DISCUSSION
Ophthalmia neonatorum is a common and well recognized clinical entity. It is frequently seen by pediatricians in the perinatal period, and it is well known to ophthalmologists. Although S. aureus is the most frequent cause for ophthalmia neonatorum, there are many other causal organisms. Staphylococcus aureus is common in the neonates' environment and may readily appear in the conjunctival sac. For many reasons it may easily become the source of the blepharo conjunctivitis of ophthalmia neonatorum.
AMERICAN JOURNAL O F OPHTHALMOLOGY 88:1052-1055, 1979
VOL. 88, NO. 6
STAPHYLOCOCCAL OPHTHALMIA NEONATRUM
The neonate produces little if any tears, has not had the opportunity to develop immunity to staphylococcal organisms, and does not benefit from the presence of lymphoid tissue in the periorbital area for protection against these organisms. Many phage types exist for S. aureus, and the production of exotoxin by the bacteria enhances its rapid infectious activity. Staphylococcal organisms are nearly ubiquitous and the neonate has an oppor tunity to come in contact with the germ by contact with the mother, other human contacts in the perinatal period, nursery environment, or at home. The lower nares may become infected and the organisms will appear on the lower eyelid and sub sequently in the conjunctiva. The time of onset of staphylococcal ophthalmia neonatorum can be any time after birth. The infection is usually rela tively mild and represents a subacute catarrhal blepharoconjunctivitis with mild discharge and conjunctival injec tion. The infection may at times become more purulent with conjunctival chemosis and eyelid edema. Ocular complica tions occasionally involve the following: staphylococcal corneal ulcers that may perforate, corneal infiltrates, hypopyon with iridocyclitis, endophthalmitis, bac terial venous thrombosis, purulent sinusi tis, empyema, pneumonia, osteomyelitis, deep abscess formation, or staphylococcal metastatic spread. The staphylococcal scalded skin syn drome is a generalized exfoliative derma titis of infants and children, associated with an infection with staphylococcal or ganisms of the phage Group 2. This syn drome was formerly known as Ritter's disease and toxic epidermal necrolysis of Lyell. This disease in its most severe form is characterized by the sudden onset of widespread reddening and tenderness of the skin followed by the exfoliation of large areas of skin so that they appear rumpled, like wet wallpaper. As the skin
1053
peels off, a dark red, painful, glistening surface is exposed. This clinical appear ance resembles the scalding caused by a burn. These changes of staphylococcal scald ed skin syndrome are the result of an infection caused by an epidermal toxin produced by the dermopathic strains of the 5. aureus bacteria. These are often, but not always, members of the phage Group 2 (Types 3A, 3B, 3C, 55, and 71). These staphylococci may be isolated from both the involved skin and the areas of the body remote to the skin eruptions. The toxin cleaves the epidermis beneath the stratum granulosum. Eruption is sometimes preceded by a relatively in nocuous staphylococcal ophthalmia neo natorum that may insidiously develop into a purulent blepharoconjunctivitis. Certain other predisposing staphylococ cal focal infections, including those of the external nares, may predispose to the de velopment of staphylococcal scalded skin syndrome as well. The cutaneous course begins with tenderness and a distinctive faint, macular, yellow orange or brick red eruption. This is characteristically dis tributed in the central portion of the face, on the neck, in the axillae, and in the groin. There is often a positive Nikolsky's sign at this time. This scarlatina-form eruption within 24 to 48 hours usually progresses to spontaneous wrinkling and large flaccid bullae characteristic of the appearance of staphylococcal scalded skin syndrome. The upper part of the epidermis separates in sheets and ribbons and the moist, erythematous base is seen. This dries quickly and recovery usually takes place within seven days, especially if antibiotic therapy is given early in the course of the disease. Localized forms of staphylococcal scalded skin syndrome occur and may be dependent upon a variety of host factors. There is an association between the infec tion with Phage Group 2 staphylococci
1054
AMERICAN JOURNAL OF OPHTHALMOLOGY
and localized bullous impetigo. There are also several reports of a scarlatina-form eruption that is also the result of an infec tion with this organism. This eruption is an abortive form that does not advance to the full exfoliative stage. The histologic examination is pathognomonic for diag nosis of staphylococcal scalded skin syn drome. This can be accomplished rapidly by examination of a frozen section of involved skin or by performing the Tzank test on involved skin areas. The larger clinical entity of "scalded skin syndrome" does have a differential diagnosis worth noting. The epidemi ology of this case, however, is typical only for staphylococcal scalded skin syn drome, and the clinical appearance is classic for that specific cause, the most common in neonates. Moreover, numer ous positive 5. aureus cultures were grown out. Bullous erythema multiforme, Leiner's disease, and bullous congenital ichthyosiform erythroderma are the much more unusual causes of infant scalded skin syndromes. Bullous erythema multiforme is rare in infants, but is caused by drug reactions, and is frequently seen in adults. This group of drugs includes anti biotics, including primarily penicillin, and, occasionally, sulfonamides, but never polymyxin B sulfate (Neosporin). Others include antipyretics, antimalarials, barbiturates, mercury, arsenic, phenylbutazone, hydantoins and phenophthalein. Our patient was not exposed to any of these. In our case, Leiner's disease was ruled out by the clinical lack of heavy scaling, a typical sign of that disease of the infant. Bullous congenital ichthyosiform eryth roderma, which is hereditary, was ruled out by a lack of evidence of familial involvement, and the short-lived course of the treated entity in our patient. That disease runs a chronic course invariably. Appropriate antibiotic management for
DECEMBER, 1979
S. aureus blepharoconjunctivitis of oph thalmia neonatorum involves appropriate early microbiologic studies including at least Gram staining and culture. Topical antibiotics are normally effective and there is no specific role for topical corticosteroids. Antibiotic sensitivities are im portant because of the frequent penicillin resistance of 5. aureus. In cases of infec tion with the more virulent strains of 5. aureus, and particularly those that are penicillin resistant, a more serious local ized blepharoconjunctivitis may develop with local sequelae, and a more rapid development of staphylococcal scalded skin syndrome may ensue. Oral or parenteral antibiotics, and in the neonatal peri od, hospitalization for more intensive management, may be indicated in these cases. Although the general prognosis for resolution of the ocular sequelae of staph ylococcal blepharoconjunctivitis, and the dermatologic sequelae of staphylococ cal scalded skin syndrome are relatively good, early diagnosis and prompt man agement are imperative. Because of the virulence of some S. aureus organisms, the variable host defenses including a lack of immunity, the variety of serious sequelae that staphylococcal infections may cause, and the lack of predictability as to the identification of which staphylo coccal infections may become particular ly virulent, casual management of possi ble staphylococcal ophthalmia neonato rum cannot be recommended. An awareness of the possible ophthalmic-dermatologic consequences of ne onatal staphylococcal infection, which initially appears as a mild catarrhal oph thalmia neonatorum of a nonspecific na ture, is imperative. Consequently, early bacteriologic evaluation should be made in all patients. Prompt management with topical antibacterial agents, and without the concurrent use of possibly exacerbat ing topical anti-inflammatory agents, is indicated. This management regimen
VOL. 88, NO. 6
STAPHYLOCOCCAL OPHTHALMIA NEONATRUM
1055
should yield rapid satisfactory resolution in most cases. Attention to the skin and recognition of the early dermatologic signs of staphylococcal scalded skin syn drome should be a part of the manage ment of ophthalmia neonatorum.
and the understanding that it may rapidly become a serious consequence of staphy lococcal ophthalmia neonatorum. We stress the need for initial microbiologic studies and early antibiotic therapy for ophthalmia neonatorum.
SUMMARY
REFERENCES
A 3-week-old infant had neonatal oph thalmia neonatorum, treated in a routine manner which rapidly developed into an advanced case of staphylococcal scalded skin syndrome. The infant had sudden onset of widespread erythematous and tender areas of skin with subsequent ex foliation of large surface areas. We em phasize the recognition of this syndrome
1. Duke-Elder, S.: Diseases of the Outer Eye. Conjunctiva. In System of Ophthalmology, vol. 8, pt. 1. London, Henry Kimpton, 1965, p p . 115-119; 154-158. 2. Melish, M. E.: The staphylococcal scalded skin syndrome. N. Engl. J. Med. 282:1114, 1970. 3. Elias, P. M., Fritsch, P., and Epstein, E. H.: Staphylococcal scalded skin syndrome. Arch. Dermatol. 113:207, 1977. 4. Lyell, A.: Toxic epidermal necrolysis. The scalded skin syndrome. J. Cont. Ed. Dermatol. 1:15, 1978.