The Journal of Dermatology Vol. 19: 556-562,1992
Actinic Cheilitis Granulomatosa Yoshinori Kuno, Shigeru Sakakibara and Nobuyuki Mizuno Abstract A granulomatous lesion of the lips caused by lNB-photosensitivity is described. A 31-year-old Japanese man developed depigmented, swollen, erythematous lips with some erosions and bloody crusts which were present for 11 months. Histologic examination revealed a dense dermal infiltration composed mainly of lymphoid-histiocytic cells. Suprabasal clefts were associated with the invasion of lymphoid cells around them. Results of patch and photopatch testing were negative. The minimal erythema dose 24 h after irradiation was lower than normal, ranging from 295 to 330 nm. The lesion was reproduced by repeated irradiation with monochromatic light of 310 and 320 nm, but not by exposure to 250, 260, 270, 280, 290, 300, or 330 nm. Topical injection of glucocorticoids and application of sunscreen led to improvement. We propose the name "actinic cheilitis granulomatosa" for this case.
Key words:
actinic cheilitis granulomatosa; cheilitis granulomatosa; lNB-photosensitivity
Introduction We report a patient who developed a granulomatous lip lesion that macroscopically resembled plasmocytosis circumorificialis and was induced by photosensitivity to lNB. Although the lesion showed a histological resemblance to actinic reticuloid, the clinical features differed. We propose "actinic cheilitis granulomatosa" to describe this case.
Case Report A 31-year-oldJapanese man noticed depigmented erythema on his lips in January of 1979, which persisted through the autumn of that year. He took doses of vitamin B 2, B6, and chlorphenilamine between September of 1979 and February of 1980, but the lesion became swollen with some erosions and crusting. He visited our dermatology department on February 25, 1980. He was an indoor worker at a chemical factory that produced urethane. There was no history of overexposure to sunlight or of any hypersensitivity or photosensiReceived December 6, 1991; accepted for publication July 14,1992. Department of Dermatology, Nagoya City University MedicalSchool, Nagoya,Japan. Reprint requests to: Yoshinori Kuno, M.D., Department of Dermatology, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan.
Fig. 1. Clinical appearance of the lips at the first visit. Reddish swollen lips with depigmented macules, erosions, and bloody crusting on the vermilion border are observed.
tivity before the lesion appeared. At his first visit, his lips were swollen and reddish. Diffuse depigmentation and large areas of erosion with bloody crusting were observed in some parts of the vermilion border (Fig. 1). Except for the lips, there were no other abnormalities on the skin or mucosa. Abnormal laboratory findings included: WBC 12,200/mm3 , band form neutrophils 62%, and lymphocytes 15%. Results of blood, stool, and urine analysis of porphyrins were normal. A volume of 0.5 ml ofl% triamcinolone acetonide was injected into the lips 7 times between April 25
Actinic Cheilitis Granulomatosa
,557
Fig. 2. Microscopic appearance of the lower lip. The epidermis shows hyperkeratosis, irregular hypergranulosis, acanthosis, and partial elongation of rete ridges. Thick crusts are observed in some areas. The most striking feature is dense infiltration into the upper and mid-dermis. Sludging can be seen throughout the dermis. The infiltrates invade the epidermis. Suprabasal clefts (arrow) and atrophy of the epidermis are seen beneath the thick crust Microabscesses of lymphoid cells can be seen around the cleft. (H&E, 10 x 2.5)
and May 30, and the swelling, erosions, and crusting decreased by the end of May. Topical application of 5% p-aminobenzoic acid in a hydrophilic ointment base as a sunscreen was applied from the end of May.Most of the patient's symptoms disappeared by earlyJune. A biopsy specimen obtained from the lower lip showed hyperkeratosis, irregular hypergranulosis, and acanthosis with partial elongation of the rete ridges in the epidermis. Thick crusts were observed in some parts, beneath which the epidermis was atrophic, forming partial suprabasal clefts. Intraepidermal invasion oflymphoid cells could be seen, especially around the clefts. A granulomatous reaclion, predominantly composed of lymphoid-histio¢)'tic cells mixed with a few plasma cells and eosinophils, occupied the upper and mid-dermis (Fig. 2). We decided to perform phototesting to determine "hether the lesions could be reproduced on challtnge. In addition, patch and photopatch testing were conducted with selected environmental and Qecupational allergens.
Methods of Phototesting, Patch, and Photopatch Testing and Results Radiation sources and detectors Three radiation systems were employed in challenge testing: System 1: Dermaray M-DMR-100 (Toshiba & Eisai, Tokyo), equipped with 7 fluorescent lamps (FL-20S' E-30,Toshiba) in parallel as the UVB light source. The main emission spectra of these lamps ranged from 275 to 375 nm with a peak at 305 nm and containing 33% UVA from 320 to 375 nm. System 2: Dermaray M-DMR-100, equipped with 14 fluorescent lamps (Flr32S . BL, Toshiba) in parallel as the UVA light source. The emission spectra of these lamps ranged from 310 to 460 nm with a peak at 350 nm. The wavelengths shorter than 320 nm were cut off by a window glass filter. System 3: An irradiation monochromator (CRM-FM type,lASCO, Tokyo), equipped with a 5 kW xenon short-arc lamp and a plane
.558
Kuno et al .10- 3 4
250
300
330
Wavelength (nm) Fig. 3. Action spectrum for erythema at 24 h after irradiation. lID: minimum and maximum limit at each wavelength in normal subjects. diffraction grating with 600 lines/mm. Halfband width was 10.4 nm and stray light was less than 0.1% at each wavelength. A uniformly irradiating system with a 6 x 6 mm irradiating area was set at the exit slit, and the irradiance uniformity measured at 320 nm was 100 ± 6.5%. A UV-Radiometer (UVR-305/365 D(II), EisaiTorex-Topcon, Tokyo) was used to measure the irradiance of systems 1 and 2. A calibrated quartz vacuum thermopile GASCa, Tokyo) combined with an amplifier and microvoltmeter GASCa) was used for system 3. Minimal erythema dose (MED) test with system 1 MED test with UVB fluorescent lamp (irradiance: 7.5 W 1m2 ) was performed on the patient's back with a circular irradiating area having a diameter of 6 mm. Graded fluences were given in mathematic increments of +2.25 x 102 j/m 2 from 2.25 x 102 to 3.6 x 103 j/m 2 • MED judged at 24 h after irradiation was 6.75 x 102 j/m 2 • The MED at 24 h after irradiation with system 1 on 10 normal subjects ranged from 6.75 x 102 to 1.8 x 103 j/m 2 • There was no abnormal elongation in the course of the erythematous reaction (1). MED test with system 2 MED test with UVA fluorescent lamp (irradiance: 5.0 x 10 W/m 2 ) was performed on the patient's back with a circular irradiating area having a diameter of 6 mm. Graded fluences were given in mathematic increments of +3.0 x
Fig. 4. Reproduction test by 2 MED irradiation with UVB fluorescent tubes (system 1) on the uninvolved skin of the patient's back. Mildly elevated erythema with papules and crusting was obtained after 8 exposures given every other day. 104 j/m 2 from 3.0 x 104 to 1.2 X 105 j/m 2• The highest dose, 1.2 x 105 j/m 2 , failed to elicit erythema either immediately or at 30 min, 24 h, 48 h, or 72 h after irradiation. This dose did not cause an erythematous reaction on 10 normal subjects either immediately or at 30 min, 24 h, 48 h, or 72 h after irradiation with system 2. Patch and pliotopatch testing Two sets of patches containing halogenated phenols, fungicides, whiteners, tar ingredients, and materials associated with the patient's occupation, including the components of urethane, were applied to the skin of his back. Patches were removed in 24 h. One set of patches was used for photopatch testing by being exposed to UVB and UVA fluorescent lamps with 2.25 x 102 j/m 2 , one-third of the MED, and 1.2 x 105 j/m 2 , respectively. The other set was not irradiated and served as conventional patch testing. The latter was evaluated at 24, 48, and 72 h after application. Photopatch test results were judged immediately, at 30 min, and at 24, 48, and 72 h after irradiation. The results were all negative. Action spectrum for erythema with system 3 Using system 3, the MED on the abdominal skin at each wavelength was measured in the range from 250 to 340 nm at 5 or 10 nm intervals. Graded fluences were given in geometric increments of +50% at each wavelength..
559
Actinic Cheilitis Granulomatosa
The MED 24 h after irradiation was below normal in the range between 295 and 330 nm (Fig. 3). Reproduction of the lesion by repeated irradiation using systems 1 and 3 The back of the patient was exposed every other day to 2 MED ofUVB using system 1 with a rectangular irradiating area of 15 x 20 mm. Mildly elevated erythema with papules and crusting was obtained after 8 exposures (Fig. 4). The same test, when performed on 3 normal subjects, produced only scaly flat erythema. Monochromatic irradiation of 2 MED in the range from 250 to 330 nm was repeated daily for 3 days on the patient's back using system 3. Scaly elevated erythema was obtained at 310 and 320 nm after 3 exposures (Fig. 5). Only flat erythema was obtained after exposure to 250, 260, 270, 280, 290, 300, or 330 nm. Three normal subjects showed only flat erythema after exposure to 250, 260, 270, 280, 290, 300 or 310 nm and no reaction to 320 or 330 nm in the same testing.
320 Fig. 5. Reproduction test with monochromatic light (system 2) on the patient's back. Scaly red papules were obtained at 310 and 320 nm after 3 daily exposures to 2 MED.
Fig. 6. Histologic picture of the lesion reproduced by repeated irradiation of 310 nm. The epidermis shows slight hyperkeratosis and irregular hypergranulosis. Diffuse infiltration into the upper dermis and dense perivascular infiltration into the mid-dermis are seen. Clefts (arrow) are seen in the lower epidermis, beneath which lymphoid cells accumulate (microabscess). (H&E, 20 x 2.5)
560
Kuno et al Table 1. Differential diagnosis of photoinduced disorders of the lip and findings in our patient: Epidemiology and etiology CAC* (Nicolau) (4)
CAC (Koten) (5)
PC** (6)
Our patient
Climate
Dry and sunny (Romania)
Dry and sunny (Kenya)
Mild (Maryland, U.SA.)
Mild (Japan)
Season
Spring to summer
Almost all yearround***
Spring to summer
All year-round
Race
Caucasian
Negro
Negro
Mongolian
Etiology
Prolonged exposure to sunlight
Prolonged exposure to sunlight
Photosensitivity
Photosensitivity Lowered MED by UVB Reproduction by 310 and 320 nm
Reproduction by sunlight *Chronic actinic cheilitis **Photosensitive cheilitis ***No marked seasonal variation exists in the highlands of Kenya.
Histologic findings of the reproduced lesions A biopsy specimen was obtained from the lesion produced by repeated irradiation of 2 MED with system 1 six days after the eighth exposure. It showed epidermal hyperkeratosis and parakeratosis. Subcomeal crusting and spongiosis were observed in some parts of the epidermis. Diffuse lymphoid-histiocytic infiltration of the upper dermis and dense perivascular infiltration of the mid-dermis were seen. Intraepidermal invasion of lymphoid cells was also observed. Infiltration of the dermis was milder than that seen in the lip lesion. A biopsy specimen was obtained from the lesion produced by repeated irradiation of 2 MED with system 3 at 310 nm 3 days after the third exposure. It showed slight hyperkeratosis and irregular hypergranulosis in the epidermis. There was diffuse lymphoid-histiocytic infiltration into the upper dermis and dense perivascular infiltration into the mid-dermis. Clefts were formed in the lower epidermis, and an invasion of lymphoid cells was observed beneath some of them. This suggested that the formation of these clefts occurred before the invasion by the lymphoid cells (Fig. 6). Discussion
This patient exhibited a granulomatous lesion only on the lips. There were several
indications of photosensitivity: the skin disorder on the lips, the therapeutic effectiveness of a sunscreen, the decrease in MED in response to lNB irradiation, and the successful reproduction of similar lesions on the uninvolved skin by repeated irradiation with lNB. Suprabasal clefts, an invasion oflymphoid cells around them, and a granulomatous reaction mainly composed of lymphoid-histiocytic cells were remarkable histological features. The findings in this patient were distinct from those of previously reported granulomatous diseases of the lips or of granulomatous photosensitivity diseases (Table 1-3). We therefore propose the diagnostic term "actinic cheilitis granulomatosa" to describe this patient. Actinic cheilitis is a chronic inflammatory disorder of the lower lip induced by prolonged exposure to sunlight during hot, dry summer weather (2-4). Our patient lives in an area of Japan with a mild climate. He had lesions on both the upper and lower lips continuously, year-round. There was no history of overexposure to sunlight. The histologic picture of chronic actinic cheilitis in Turkey was subacute to chronic inflammation (3). Its characteristics included a thickened superficial layer (acanthosis) with mild perivascular infiltration in the superficial tunica propria. In the late stages, the formation of thick crusts, edematous swelling
Actinic Cheilitis Granulomatosa
561
Table 2. Differential diagnosis of photoinduced disorders of the lip and findings in our patient: Clinical course, features, and treatment CAC (Nicolau)
CAC (Koten)
PC
Our patient
Course
Prolonged
Prolonged
Prolonged
1 year*
Location
Lower lip
Central portion of the lower lip
Lower lip
The entire upper and lower lip
Clinical features Swelling Fissures Ulceration Crusting Depigmentation Scaling
±
+ + +
Topical steroid
?
?
Ineffective (Ointment)
Effective (Injection)
Sunscreen
?
?
Effective
Effective
±
++ ++ + ++
++
.+ +
±
-** ++ +
*Because he was well controlled. **The patient showed erosion, not ulceration. Table 3. Differential diagnosis of photoinduced disorders of the lip and findings in our patient: Histological features CAC (Nicolau)
CAC (Koten)
PC
Our patient
+ + +
+ + +
+
+
+
+
+
+ +
Epidermis Hyperkeratosis Parakeratosis Acanthosis Hypergranulosis Ulceration Cellular atypia Suprabasal cleft
+*
+ PMN
Intraepidennal invasion Infiltrate Lymphoid-histiocytic cell Plasma cell PMN
Various degrees +
Basophilic degeneration
±
Lymphoid cell
Band-like + +++
Dense
±
±
+ +++
Dense +++
± ±
+++
*Observed in an advanced stage
ef the papilla, and an increased number of
Actinic Cheilitis Granulomatosa Yoshinori Kuno, Shigeru Sakakibara and Nobuyuki Mizuno Abstract A granulomatous lesion of the lips caused by lNB-photosensitivity is described. A 31-year-old Japanese man developed depigmented, swollen, erythematous lips with some erosions and bloody crusts which were present for 11 months. Histologic examination revealed a dense dermal infiltration composed mainly of lymphoid-histiocytic cells. Suprabasal clefts were associated with the invasion of lymphoid cells around them. Results of patch and photopatch testing were negative. The minimal erythema dose 24 h after irradiation was lower than normal, ranging from 295 to 330 nm. The lesion was reproduced by repeated irradiation with monochromatic light of 310 and 320 nm, but not by exposure to 250, 260, 270, 280, 290, 300, or 330 nm. Topical injection of glucocorticoids and application of sunscreen led to improvement. We propose the name "actinic cheilitis granulomatosa" for this case.
Key words:
actinic cheilitis granulomatosa; cheilitis granulomatosa; lNB-photosensitivity
Introduction We report a patient who developed a granulomatous lip lesion that macroscopically resembled plasmocytosis circumorificialis and was induced by photosensitivity to lNB. Although the lesion showed a histological resemblance to actinic reticuloid, the clinical features differed. We propose "actinic cheilitis granulomatosa" to describe this case.
Case Report A 31-year-oldJapanese man noticed depigmented erythema on his lips in January of 1979, which persisted through the autumn of that year. He took doses of vitamin B 2, B6, and chlorphenilamine between September of 1979 and February of 1980, but the lesion became swollen with some erosions and crusting. He visited our dermatology department on February 25, 1980. He was an indoor worker at a chemical factory that produced urethane. There was no history of overexposure to sunlight or of any hypersensitivity or photosensiReceived December 6, 1991; accepted for publication July 14,1992. Department of Dermatology, Nagoya City University MedicalSchool, Nagoya,Japan. Reprint requests to: Yoshinori Kuno, M.D., Department of Dermatology, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan.
Fig. 1. Clinical appearance of the lips at the first visit. Reddish swollen lips with depigmented macules, erosions, and bloody crusting on the vermilion border are observed.
tivity before the lesion appeared. At his first visit, his lips were swollen and reddish. Diffuse depigmentation and large areas of erosion with bloody crusting were observed in some parts of the vermilion border (Fig. 1). Except for the lips, there were no other abnormalities on the skin or mucosa. Abnormal laboratory findings included: WBC 12,200/mm3 , band form neutrophils 62%, and lymphocytes 15%. Results of blood, stool, and urine analysis of porphyrins were normal. A volume of 0.5 ml ofl% triamcinolone acetonide was injected into the lips 7 times between April 25
Actinic Cheilitis Granulomatosa
,557
Fig. 2. Microscopic appearance of the lower lip. The epidermis shows hyperkeratosis, irregular hypergranulosis, acanthosis, and partial elongation of rete ridges. Thick crusts are observed in some areas. The most striking feature is dense infiltration into the upper and mid-dermis. Sludging can be seen throughout the dermis. The infiltrates invade the epidermis. Suprabasal clefts (arrow) and atrophy of the epidermis are seen beneath the thick crust Microabscesses of lymphoid cells can be seen around the cleft. (H&E, 10 x 2.5)
and May 30, and the swelling, erosions, and crusting decreased by the end of May. Topical application of 5% p-aminobenzoic acid in a hydrophilic ointment base as a sunscreen was applied from the end of May.Most of the patient's symptoms disappeared by earlyJune. A biopsy specimen obtained from the lower lip showed hyperkeratosis, irregular hypergranulosis, and acanthosis with partial elongation of the rete ridges in the epidermis. Thick crusts were observed in some parts, beneath which the epidermis was atrophic, forming partial suprabasal clefts. Intraepidermal invasion oflymphoid cells could be seen, especially around the clefts. A granulomatous reaclion, predominantly composed of lymphoid-histio¢)'tic cells mixed with a few plasma cells and eosinophils, occupied the upper and mid-dermis (Fig. 2). We decided to perform phototesting to determine "hether the lesions could be reproduced on challtnge. In addition, patch and photopatch testing were conducted with selected environmental and Qecupational allergens.
Methods of Phototesting, Patch, and Photopatch Testing and Results Radiation sources and detectors Three radiation systems were employed in challenge testing: System 1: Dermaray M-DMR-100 (Toshiba & Eisai, Tokyo), equipped with 7 fluorescent lamps (FL-20S' E-30,Toshiba) in parallel as the UVB light source. The main emission spectra of these lamps ranged from 275 to 375 nm with a peak at 305 nm and containing 33% UVA from 320 to 375 nm. System 2: Dermaray M-DMR-100, equipped with 14 fluorescent lamps (Flr32S . BL, Toshiba) in parallel as the UVA light source. The emission spectra of these lamps ranged from 310 to 460 nm with a peak at 350 nm. The wavelengths shorter than 320 nm were cut off by a window glass filter. System 3: An irradiation monochromator (CRM-FM type,lASCO, Tokyo), equipped with a 5 kW xenon short-arc lamp and a plane
.558
Kuno et al .10- 3 4
250
300
330
Wavelength (nm) Fig. 3. Action spectrum for erythema at 24 h after irradiation. lID: minimum and maximum limit at each wavelength in normal subjects. diffraction grating with 600 lines/mm. Halfband width was 10.4 nm and stray light was less than 0.1% at each wavelength. A uniformly irradiating system with a 6 x 6 mm irradiating area was set at the exit slit, and the irradiance uniformity measured at 320 nm was 100 ± 6.5%. A UV-Radiometer (UVR-305/365 D(II), EisaiTorex-Topcon, Tokyo) was used to measure the irradiance of systems 1 and 2. A calibrated quartz vacuum thermopile GASCa, Tokyo) combined with an amplifier and microvoltmeter GASCa) was used for system 3. Minimal erythema dose (MED) test with system 1 MED test with UVB fluorescent lamp (irradiance: 7.5 W 1m2 ) was performed on the patient's back with a circular irradiating area having a diameter of 6 mm. Graded fluences were given in mathematic increments of +2.25 x 102 j/m 2 from 2.25 x 102 to 3.6 x 103 j/m 2 • MED judged at 24 h after irradiation was 6.75 x 102 j/m 2 • The MED at 24 h after irradiation with system 1 on 10 normal subjects ranged from 6.75 x 102 to 1.8 x 103 j/m 2 • There was no abnormal elongation in the course of the erythematous reaction (1). MED test with system 2 MED test with UVA fluorescent lamp (irradiance: 5.0 x 10 W/m 2 ) was performed on the patient's back with a circular irradiating area having a diameter of 6 mm. Graded fluences were given in mathematic increments of +3.0 x
Fig. 4. Reproduction test by 2 MED irradiation with UVB fluorescent tubes (system 1) on the uninvolved skin of the patient's back. Mildly elevated erythema with papules and crusting was obtained after 8 exposures given every other day. 104 j/m 2 from 3.0 x 104 to 1.2 X 105 j/m 2• The highest dose, 1.2 x 105 j/m 2 , failed to elicit erythema either immediately or at 30 min, 24 h, 48 h, or 72 h after irradiation. This dose did not cause an erythematous reaction on 10 normal subjects either immediately or at 30 min, 24 h, 48 h, or 72 h after irradiation with system 2. Patch and pliotopatch testing Two sets of patches containing halogenated phenols, fungicides, whiteners, tar ingredients, and materials associated with the patient's occupation, including the components of urethane, were applied to the skin of his back. Patches were removed in 24 h. One set of patches was used for photopatch testing by being exposed to UVB and UVA fluorescent lamps with 2.25 x 102 j/m 2 , one-third of the MED, and 1.2 x 105 j/m 2 , respectively. The other set was not irradiated and served as conventional patch testing. The latter was evaluated at 24, 48, and 72 h after application. Photopatch test results were judged immediately, at 30 min, and at 24, 48, and 72 h after irradiation. The results were all negative. Action spectrum for erythema with system 3 Using system 3, the MED on the abdominal skin at each wavelength was measured in the range from 250 to 340 nm at 5 or 10 nm intervals. Graded fluences were given in geometric increments of +50% at each wavelength..
559
Actinic Cheilitis Granulomatosa
The MED 24 h after irradiation was below normal in the range between 295 and 330 nm (Fig. 3). Reproduction of the lesion by repeated irradiation using systems 1 and 3 The back of the patient was exposed every other day to 2 MED ofUVB using system 1 with a rectangular irradiating area of 15 x 20 mm. Mildly elevated erythema with papules and crusting was obtained after 8 exposures (Fig. 4). The same test, when performed on 3 normal subjects, produced only scaly flat erythema. Monochromatic irradiation of 2 MED in the range from 250 to 330 nm was repeated daily for 3 days on the patient's back using system 3. Scaly elevated erythema was obtained at 310 and 320 nm after 3 exposures (Fig. 5). Only flat erythema was obtained after exposure to 250, 260, 270, 280, 290, 300, or 330 nm. Three normal subjects showed only flat erythema after exposure to 250, 260, 270, 280, 290, 300 or 310 nm and no reaction to 320 or 330 nm in the same testing.
320 Fig. 5. Reproduction test with monochromatic light (system 2) on the patient's back. Scaly red papules were obtained at 310 and 320 nm after 3 daily exposures to 2 MED.
Fig. 6. Histologic picture of the lesion reproduced by repeated irradiation of 310 nm. The epidermis shows slight hyperkeratosis and irregular hypergranulosis. Diffuse infiltration into the upper dermis and dense perivascular infiltration into the mid-dermis are seen. Clefts (arrow) are seen in the lower epidermis, beneath which lymphoid cells accumulate (microabscess). (H&E, 20 x 2.5)
560
Kuno et al Table 1. Differential diagnosis of photoinduced disorders of the lip and findings in our patient: Epidemiology and etiology CAC* (Nicolau) (4)
CAC (Koten) (5)
PC** (6)
Our patient
Climate
Dry and sunny (Romania)
Dry and sunny (Kenya)
Mild (Maryland, U.SA.)
Mild (Japan)
Season
Spring to summer
Almost all yearround***
Spring to summer
All year-round
Race
Caucasian
Negro
Negro
Mongolian
Etiology
Prolonged exposure to sunlight
Prolonged exposure to sunlight
Photosensitivity
Photosensitivity Lowered MED by UVB Reproduction by 310 and 320 nm
Reproduction by sunlight *Chronic actinic cheilitis **Photosensitive cheilitis ***No marked seasonal variation exists in the highlands of Kenya.
Histologic findings of the reproduced lesions A biopsy specimen was obtained from the lesion produced by repeated irradiation of 2 MED with system 1 six days after the eighth exposure. It showed epidermal hyperkeratosis and parakeratosis. Subcomeal crusting and spongiosis were observed in some parts of the epidermis. Diffuse lymphoid-histiocytic infiltration of the upper dermis and dense perivascular infiltration of the mid-dermis were seen. Intraepidermal invasion of lymphoid cells was also observed. Infiltration of the dermis was milder than that seen in the lip lesion. A biopsy specimen was obtained from the lesion produced by repeated irradiation of 2 MED with system 3 at 310 nm 3 days after the third exposure. It showed slight hyperkeratosis and irregular hypergranulosis in the epidermis. There was diffuse lymphoid-histiocytic infiltration into the upper dermis and dense perivascular infiltration into the mid-dermis. Clefts were formed in the lower epidermis, and an invasion of lymphoid cells was observed beneath some of them. This suggested that the formation of these clefts occurred before the invasion by the lymphoid cells (Fig. 6). Discussion
This patient exhibited a granulomatous lesion only on the lips. There were several
indications of photosensitivity: the skin disorder on the lips, the therapeutic effectiveness of a sunscreen, the decrease in MED in response to lNB irradiation, and the successful reproduction of similar lesions on the uninvolved skin by repeated irradiation with lNB. Suprabasal clefts, an invasion oflymphoid cells around them, and a granulomatous reaction mainly composed of lymphoid-histiocytic cells were remarkable histological features. The findings in this patient were distinct from those of previously reported granulomatous diseases of the lips or of granulomatous photosensitivity diseases (Table 1-3). We therefore propose the diagnostic term "actinic cheilitis granulomatosa" to describe this patient. Actinic cheilitis is a chronic inflammatory disorder of the lower lip induced by prolonged exposure to sunlight during hot, dry summer weather (2-4). Our patient lives in an area of Japan with a mild climate. He had lesions on both the upper and lower lips continuously, year-round. There was no history of overexposure to sunlight. The histologic picture of chronic actinic cheilitis in Turkey was subacute to chronic inflammation (3). Its characteristics included a thickened superficial layer (acanthosis) with mild perivascular infiltration in the superficial tunica propria. In the late stages, the formation of thick crusts, edematous swelling
Actinic Cheilitis Granulomatosa
561
Table 2. Differential diagnosis of photoinduced disorders of the lip and findings in our patient: Clinical course, features, and treatment CAC (Nicolau)
CAC (Koten)
PC
Our patient
Course
Prolonged
Prolonged
Prolonged
1 year*
Location
Lower lip
Central portion of the lower lip
Lower lip
The entire upper and lower lip
Clinical features Swelling Fissures Ulceration Crusting Depigmentation Scaling
±
+ + +
Topical steroid
?
?
Ineffective (Ointment)
Effective (Injection)
Sunscreen
?
?
Effective
Effective
±
++ ++ + ++
++
.+ +
±
-** ++ +
*Because he was well controlled. **The patient showed erosion, not ulceration. Table 3. Differential diagnosis of photoinduced disorders of the lip and findings in our patient: Histological features CAC (Nicolau)
CAC (Koten)
PC
Our patient
+ + +
+ + +
+
+
+
+
+
+ +
Epidermis Hyperkeratosis Parakeratosis Acanthosis Hypergranulosis Ulceration Cellular atypia Suprabasal cleft
+*
+ PMN
Intraepidennal invasion Infiltrate Lymphoid-histiocytic cell Plasma cell PMN
Various degrees +
Basophilic degeneration
±
Lymphoid cell
Band-like + +++
Dense
±
±
+ +++
Dense +++
± ±
+++
*Observed in an advanced stage
ef the papilla, and an increased number of
