Objective. Blue light phototherapy is commonly administered to neonates as treatment of indirect hyperbilirubinemia, often in conjunction with blood transfusions to treat hemolytic anemia. We observed a distinctive cutaneous complication of phototherapy in six neonates with hyperbilirubinemia.
Methodology. We studied the clinical and histologic characteristics of the eruption, as well as the porphyrin levels in affected neonates. Five of the patients had erythroblastosis fetalis; the other had profound anemia from twin–twin transfusion. All of the neonates developed purpuric patches at sites of maximal exposure to the phototherapy lights, with dramatic sparing at shielded sites within 24 hours after initiation of the phototherapy. On discontinuation of phototherapy, all eruptions cleared within 1 week. Examination of skin biopsy sections showed purpura without significant inflammation or keratinocyte necrosis. Plasma porphyrins (copro- and proto-) were elevated in the two patients in which they were assessed.
Conclusions. The distribution of the eruption in areas exposed to light and presence of circulating porphyrins suggest that porphyrinemia may underlie the light-induced purpuric eruption. Additional studies will be required to determine definitively the mechanisms of both the purpuric phototherapy-induced eruption and the development of increased blood porphyrin levels in these transfused neonates.
Erythroblastosis fetalis has been associated with several cutaneous manifestations, particularly jaundice, cutaneous edema, pallor, and extramedullary dermal erythropoiesis.1Blue light phototherapy is usually administered to diminish the associated jaundice, and exchange transfusion is undertaken if the manifestations of incompatibility are severe. We describe six neonates who developed purpuric phototherapy-induced eruption, a raspberry-colored eruption at cutaneous sites of maximal exposure to the phototherapy lights, with sparing at shielded sites. Five of the neonates had erythroblastosis fetalis; the other had profound anemia and hyperbilirubinemia without blood group incompatibility (Table)1. Transfusions were administered and phototherapy was instituted within 24 hours of birth in each neonate. The photodistributed eruption appeared within 4 days after institution of the lights and cleared spontaneously within 1 week after discontinuation. Inspection of the daylight fluorescent phototherapy lights in each patient showed full shielding to be in place.
A girl, weighing 2480 g, was born after 35 weeks' gestation to an O-positive mother. Amniocentesis had been performed at 3 months' gestational age, and the Coombs test result on the mother was negative at that time. The infant was noted to be pale at birth, with an initial hemoglobin of 5.2 g%, hematocrit 16%, reticulocyte count of 24%, and platelet count of 153 000. The infant's blood type was determined to be O-positive, with anti-c and anti-E antibodies, and 4+ Coombs-positivity. By 10 hours of age, the total bilirubin level was 15.1 mg/dL, with a direct component of 1.7 mg/dL. Double-bank phototherapy was initiated, and the neonate was administered two transfusions of packed red blood cells to treat the anemia. Total bilirubin levels had increased during 2 days to a peak of 27.6 mg/dL, with a direct bilirubin level of 7.9 mg/dL. Two exchange transfusions were performed, with continued double-bank phototherapy for control.
Two days after birth, a raspberry-colored nonblanching eruption was noted on the trunk at sites of exposure to the lights, with total sparing of areas underlying monitor leads and the temperature probe (Fig 1). Histopathologic evaluation of lesional skin biopsy showed extravasated red blood cells without significant inflammatory infiltrates. Despite mild epidermal spongiosis, keratinocyte necrosis was notably absent (Fig 2). Periodic-acid Schiff stains showed no deposits of positive material in the blood vessel walls. The patient never developed thrombocytopenia. The direct bilirubin level peaked at 7.9 mg/dL at 3 days of age, but transaminases were normal. Studies for porphyrin levels were not performed. The patient had not been administered any photosensitizing drugs, including furosemide, before the onset of the eruption. The eruption never became vesiculobullous, and it spontaneously resolved within 2 days after discontinuation of the phototherapy, without any cutaneous sequelae.
During a follow-up period of 6 years, the patient developed no skin problems. However, she has developmental delay with moderate to severe sensorineural hearing loss, attributable to kernicterus. She also developed insulin-dependent diabetes mellitus at 1 year of age.
A 3015-g boy was born after 37 weeks' gestation to an A-negative mother who was known to have problems with Rh isoimmunization. At birth, the infant was pale and tachycardic, with poor respiratory effort and hepatomegaly to the level of the umbilicus. Initial hemoglobin was 10.7 g%, with a platelet count of 60 000 and a reticulocyte count of 51.2%. Cord total bilirubin level was 11.4 mg/dL, with a direct level of 2.8 mg/dL. Phototherapy lights were begun immediately, but the total bilirubin escalated to 22.2 mg/dL by 12 hours of life. When the respiratory status stabilized at 20 hours of life, an exchange transfusion was performed, with a preexchange bilirubin level of 26.4 mg/dL total and 9.8 mg/dL direct. The direct bilirubin level continued to be elevated markedly throughout hospitalization, but transaminases were normal.
At 3 days of age, the infant first developed a raspberry-colored nonblanching rash on the chest, abdomen, and right arm. The skin appeared normal where cardiac leads had been placed (Fig3). A skin biopsy was refused. Urinary and plasma porphyrin levels were measured by Corning (Corning, New York) and SmithKline Beecham Clinical Laboratories (St Louis, MO), respectively.2,3 Urine porphyrin levels were reportedly normal, including coproporphyrin levels, although only 40 mL was collected during a 24-hour period (data on creatinine clearance during that time not available). Plasma coproporphyrin levels were 13 μg/dL (normal, ≤1 μg/dL), and protoporphyrin and other porphyrin levels were normal. The purpuric eruption resolved 3 days after discontinuation of the phototherapy. During a follow-up period of 4 years, the infant has had no additional medical problems.
A 3550-g boy was born after 35 weeks' gestation to an A-negative mother. Despite Rhogam administration at 28 weeks' gestation, the pregnancy was complicated by known sensitization tod-antigen. Ascites and pericardial effusion were detected by ultrasound at 35 weeks' gestation, and cesarean section was performed. The infant was severely edematous and pale, with an initial hemoglobin of 3.7 g% and a total bilirubin level of 7.0 mg/dL. The infant was transfused with packed erythrocytes, and double-bank phototherapy was initiated at 11 hours of age. The perinatal course was complicated by profound acidosis, congestive heart failure treated once with furosemide, anemia, and thrombocytopenia requiring platelet transfusion. A purpuric eruption on the chest, abdomen, and chin, with striking sparing at sites of leads and dressings, was first noted 26 hours after initiation of phototherapy. Lights were checked and found to have a normal fluency of 8 to 9 mJ/cm.2 At that time, total bilirubin level was 13.7 mg/dL, with a direct component of 4.2 mg/dL. Transaminase levels were elevated [SGOT, 258 U/L (normal, 0 to 30 U/L); SGPT, 91 U/L (normal, 0 to 25 U/L)]. Plasma coproporphyrin and protoporphyrin levels were 6.6 μg/dL and 16.9 μg/dL, respectively (normal, <1 μg/dL) (SmithKline Beecham Clinical Laboratories). Total erythrocyte porphyrin was slightly increased at 111 μg/dL (normal, 16 to 60 μg/dL) (Mayo Clinic Laboratories, Rochester, NY). Urinary porphyrin levels were normal (Corning Clinical Laboratories).2,3 Histologic examination of a lesional skin biopsy showed extravasated red blood cells with a mild lymphocytic dermal infiltrate but no keratinocyte necrosis. Periodic-acid Schiff stains revealed no deposits of material within the blood vessel walls.
Phototherapy was discontinued 32 hours after initiation and 6 hours after the eruption appeared. The eruption had cleared considerably within 2 days and totally by 7 days after discontinuation. At 2 months of age, free erythrocyte protoporphyrins were still increased to 55 μg/dL (normal, <35 μg/dL) (SmithKline Beecham Laboratories), and urine porphyrin levels were normal (data on plasma levels not obtained). At that time, transaminases and bilirubin values were still elevated (SGOT, 74 U/L; SGPT, 91 U/L; total bilirubin, 2.3 mg/dL; direct bilirubin, 1.0 mg/dL). Levels of plasma porphyrins and direct bilirubin were normal at 4 months of age, although the SGOT (110 U/L), SGPT (116 U/L), and total bilirubin (1.4 mg/dL) levels were slightly elevated.
Visible light phototherapy is the treatment of choice for neonatal indirect hyperbilirubinemia.4 Daylight fluorescent bulbs emit radiance in a continuous emission spectrum from 320 nm to 700 nm, although the therapeutic wavelength is in the blue range. Shielding is included with phototherapy units to protect the infant from bulb breakage and from radiation wavelengths <380 nm during phototherapy.5
In this report, we describe a benign but distinct complication of phototherapy in six neonates. The characteristic clinical features of the eruption are clear demarcation, failure to blanch with diascopy, localization of purpura to sites closest to the phototherapy lamps, sparing of sites protected from phototherapy exposure, and clearing of the eruption with discontinuation of phototherapy. These features implicate the phototherapy lamps in triggering the cutaneous disorder. The relatively rare complication in transfused neonates that we call “purpuric phototherapy-induced eruption” was seen in these six neonates during a 6-year period at three different neonatal units within the Northwestern University Medical School system (five neonates) and at Children's Hospital of Philadelphia. All of these neonates received transfusions before exposure to the lights; in five of the six infants, erythroblastosis fetalis was the cause of the hemolytic anemia, whereas in the fifth, a twin–twin transfusion necessitated the blood transfusion.
The pattern of the eruption led to the initial consideration of “burn” as the diagnosis in several of these infants, yet no reason for a burn could be determined. Siegfried et al described two neonates who were treated with fluorescent daytime lamps without Plexiglass shielding.6 In both patients, “erythema” (not a purpuric eruption) was noted at exposed sites, with sparing; blistering was noted in one of these infants, consistent with a second degree burn. Neither neonate received a transfusion, and no skin biopsy was performed. Although the nonblanching nature of the phototherapy-induced purpura differs from the “sunburn” of ultraviolet A exposure from the fluorescent lamps, we specifically checked the shielding in all of the infants and found it to be in place. In each of our neonatal units, standard shielding for the phototherapy units is never removed, and the same units have been used by hundreds of other babies without complication. Furthermore, the biopsy examination of lesional skin of patients 1 and 3 showed focal areas of purpura without features of cutaneous ultraviolet burn (significant epidermal edema, necrotic keratinocytes, or inflammatory infiltration). We also considered the diagnosis of a heat-mediated burn. However, the lack of involvement of the skin in contact with the central metal area of the leads and the lack of epidermal damage and inflammation in the biopsy make this diagnosis unlikely.
Well-demarcated erythematous photosensitivity eruptions and purpuric lesions with sparing of shielded areas may result from the administration of phototoxic drugs and exposure to ultraviolet A radiation. The possibility of a drug-induced reaction must be considered in the neonate with phototherapy purpura. Most notorious among these photosensitizing drugs is furosemide,7 a medication commonly administered to sick neonates. Three of our six neonates were exposed to furosemide before the onset of the eruption. Administration of dyes may also cause photosensitivity. Intravenous fluorescein administration for angiography in a 32-week gestational age neonate resulted in a “partial thickness burn” after exposure to phototherapy for hyperbilirubinemia.8 The eruption was described as “erythematous and vesicular . . . with bullae.” Areas under leads were spared. The skin lesions were attributed to phototoxicity from the fluorescein, which has been shown to produce photosensitization by generation of a superoxide anion when exposed to light at a wavelength of 480 nm, in the visible light range. Slow renal clearance of the fluorescein may have led to its persistence in the skin for 6 days rather than for the usual 12 to 18 hours, as detected by Wood's lamp. In this neonate with necrotizing enteritis and surgical intervention, transfusions were likely to have been administered. Blanching of the “erythema” with compression of skin is not mentioned, nor were porphyrin levels obtained.
Although the mechanism of phototherapy purpura in our six neonates is unknown, it is intriguing to consider the possibility of circulating porphyrins as the causative agents. Porphyrins absorb light maximally in the Soret band (400 to 410 nm), with lesser bands occurring in the long visible range (580 to 650 nm).9 Photodistributed cutaneous erythema with purpura developed in a liver transplant recipient after exposure to a heat lamp that emitted visible light.10 Blood levels of both coproporphyrins and protoporphyrins were elevated at the time of the eruption. Neonatal blistering and photosensitivity during phototherapy for jaundice have been described in infants with congenital erythropoietic porphyria,11,12 and purpura is an occasional feature of erythropoietic protoporphyria. Photodistributed erythema has been described occasionally in neonates treated with the experimental compound tin-protoporphyrin followed by daylight fluorescent phototherapy to treat hyperbilirubinemia,13 which cleared after discontinuation of the phototherapy.
Crawford et al recently described a neonate with erythroblastosis attributable to antibodies against maternal e andc blood antigens who developed a “violaceous discoloration . . . with sharp demarcation at sites of photoprotection” 31 hours after initiation of phototherapy.14 The appearance of this eruption was identical to that in our six neonates. In contrast, however, Crawford et al's patient also developed erosions at maximally affected sites and required 3 weeks to clear after discontinuation of the phototherapy. Laboratory tests on this baby showed markedly elevated levels of free erythrocyte protoporphyrin on the fifth day of life and zinc protoporphyrin levels on the 14th and 31st days; erythrocyte protoporphyrin levels were normal at 19 weeks of age. Plasma coproporphyrin levels were not described.
Blisters and erosions have been described recently in another neonate with hemolytic disease of the newborn who received phototherapy.15 This neonate had normal urine, fecal, and erythrocyte porphyrin levels, but had elevated plasma porphyrin levels [(peak total porphyrin, 27.3 μg/dL on day 15 (normal, <1 μg/dL)] when first measured 4 days after the blisters appeared. This elevated plasma porphyrin level was largely attributable to elevated plasma coproporphyrins. Similarly, the plasma porphyrin level, largely comprised of coproporphyrins, was elevated in two neonates described in our report in whom levels were obtained. Normally, plasma porphyrins are below the level of detection. Levels in the range of 10 to 15 μg/dL are usually associated with cutaneous photosensitivity, eg, the mean plasma porphyrin level in porphyria cutanea tarda is 15.8 ± 9.1 μg/dL (predominantly plasma coproporphyrins).16
The origin of the increased plasma porphyrins in the neonates that we describe is unclear. Hepatic cholestasis and poor hepatic porphyrin metabolism may have contributed to the increase in plasma porphyrins, because the direct bilirubin level was elevated in the two patients with increased plasma porphyrins. One of these patients also had an increase in transaminase levels. However, patient 3 and a patient described previously14 showed elevated erythrocyte porphyrins, which cannot be explained by hepatic dysfunction. It is unlikely that the transfused blood contained elevated levels of porphyrins. On the other hand, an unlikely but possible source of circulating porphyrins is release of porphyrins by hemolysis of young erythrocyte precursors, including reticulocytes, which contain at least a 10-fold higher protoporphyrin concentration than do mature erythrocytes.17
Purpuric light eruption should be recognized as a transient, benign, cutaneous eruption in transfused neonates who undergo phototherapy. Our discovery of significantly increased plasma porphyrin levels in the two neonates studied suggests a link with the development of cutaneous lesions after exposure to intense fluorescent radiation in the range of 400 nm. Examination of the plasma porphyrin levels in neonates affected in the future may help to elucidate the mechanism of this distinct purpuric eruption.
We thank Johnson & Johnson Consumer Products Inc for the the generous support that allowed the publication of color photographs. We also thank Maureen Poh-Fitzpatrick, MD, for her thoughtful review of the manuscript.
- Received December 2, 1996.
- Accepted January 21, 1997.
- Address correspondence to Amy S. Paller, MD, Division of Dermatology #107, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614.
Dr Cunningham is currently a Johnson & Johnson fellow in pediatric dermatology.
- SGOT =
- serum glutamate oxalacetate transaminase •
- SGPT =
- serum glutamate pyruvate transaminase
- Ford RE,
- Ou C-N,
- Ellefson RD
- ↵Labbe RF, Lamon JM. Porphyrins and disorders of porphyrin metabolism. In: Tietz NW, ed. Textbook of Clinical Chemistry. Philadelphia, PA: WB Saunders Co, 1986:1589–1614
- Polin RA
- Kappas A,
- Drummond GS,
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- Copyright © 1997 American Academy of Pediatrics