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Dual porphyria: a case of acute intermittent porphyria in association with porphyria cutanea tarda, and a four year follow up1
P526
P528
DUAL PORPHYRIA: A CASE OF ACUTE INTERMITTENT PORPHYRIA IN ASSOCIATION WITH PORPHYRIA CUTANEA TARDA, AND A FOUR YEAR FOLLOW UP. Jason DL Williams, MBChB, Manchester University, Manchester, England, Russell Ead, MD, Manchester University, Manchester, England, Brian Kirby, MD, Manchester University, Manchester, England, Felicity Stewart, MBBS, MD, Department of Biochemistry, Hope Hospital, Manchester, England There are only four cases reported of acute intermittent porphyria (AIP) in association with porphyria cutanea tarda (PCT). Enzyme studies in these patients revealed a dual deficiency, with decreased activity of both porphobilinogen deaminase as seen in AIP and uroporphyrinogen decarboxylase, as seen in PCT. To date there have been no reports of treatment or follow up of these patients. A 48 year old lady was referred to dermatology in 1999 with a two week history of haemorrhagic blisters on the hands and feet after a holiday in Corfu. She had been diagnosed with AIP at the age of 17, having complained of abdominal pain and paraesthesia in the fingers and toes. The gene mutation causing this was subsequently identified by Professor Elder (University of Cardiff). She had had a hysterectomy at age 30 and had taken HRT since age 35. She had undergone bone marrow transplant aged 37 for acute myeloid leukaemia, and subsequently developed blisters on her feet and ears, which settled within a few weeks. She was taking Beta Blockers for hypertension. There was no family history of porphyria. Examination revealed tense non-haemorrhagic blisters on the dorsum of fingers, hands and toes. Investigations revealed elevated aminolaevulinic acid, porphobilinogen, uroporphyrin and 7-carboxyporphyrin with normal coproporphyrin. The results were consistent with a diagnosis of both porphyria cutanea tarda and acute intermittent porphyria. Plasma porphyrin screen was positive with a maximum emission at 618 nm. She has subsequently developed mild renal impairment and liver biopsy showed iron deposition. The HRT was stopped as estrogen can exacerbate both PCT and AIP, but she was unable to cope without it, because of menopausal symptoms. She was recommended oral supplements to aid weight gain and was subsequently treated unsuccessfully with hydroxychloroquine. She then underwent a course of bi-weekly venesection (total 11 units removed). This resulted in an improvement in symptoms and a marked decrease in ferritin and iron saturation levels. This case illustrates the complexity in managing patients with dual deficiency porphyrias, and reminds dermatologists of the long-term sequelae of these conditions.
CHANGES OF SKIN SURFACE TEMPERATURE INFLUENCE UV-INDUCED ACUTE HUMAN SKIN REACTION IN VIVO Oh Sang Kwon, MD, Seoul National University Hospital, Seoul, Korea, Eun Ju Hwang, MD, Seoul National University Hospital, Seoul, Korea, Seong Jin Jo, MD, Seoul National University Hospital, Seoul, Korea, Jin Ho Chung, MD, Seoul National University Hospital, Seoul, Korea Skin surface temperature at ultraviolet (UV) exposure would influence acute skin reactions such as erythema and pigmentation. Thermal changes before or after UV irradiation could influence the skin response in the way to change vascular blood flow and inflammatory response. In this study our aim was to investigate the influence of thermal changes on UV-induced acute skin reaction with relatively objective and quantitative method. Our volunteers consisted of 10 males ranging in age from 22 to 24 years with Fitzpatrick’s skin type III or IV. A sunlight fluorescent sunlamp (Waldmann UV 800) was used as a UVB light source. Either of Heat application with 45℃ heating pad or cold application with ice pack for 1 hour was done before or after UVB irradiation (control, 0.5MED, 1MED, 2MED) and then skin color was determined with Mexameter and Minolta Spectrophotometer CM-2002 for two weeks (Day 1, 3, 7, 14). The results were presented by the Erythema/Melanin indices (EI/MI) and L*a*b* system recommended by the CIE (Commission internationale de l’Eclairage). ITA (Individual Typology Angle) is also thought to be a quantitative and objective value of classifying individual skin color. In this study, compared with the only UV-exposed control, surface temperature modified groups showed generally higher Erythema Indices and a* values plus lower L*, b* values with lower UV exposure (0.5 and 1 MED). In the higher UV exposure groups of 2 MED, post-heating (UV3 Heating) and pre-cooling (Cold3 UV) groups tended to show gradually smaller MI and a* values plus higher L* and ITA values and than control in contrast to pre-heating group(Heat3 UV) and post-cooling (UV3 Cold) groups with the lower L*, ITA values and higher a* values than control. All the temperature-modified groups with any UV-irradiation showed relatively lower b* values than control. Our results indicate that alteration of the skin surface temperature modulates the degree of UV-induced acute reaction such as erythema and pigmentation. 2 MED has been suggested as the most adequate dose to assess UV-induced skin reaction in Oriental skin. In our subjects exposed to this dose, post-heating and pre-cooling showed relatively less erythema and pigmentation than other groups. These interactions between UV exposure and skin surface temperature should be considered to study the effects of natural sun exposure in routine life and to research in the field of photoprotection or UV-phototherapy.
Disclosure not available at press time.
Disclosure not available at press time.
P527 ORAL POLYPODIUM LEUCOTOMOS EXTRACT PROTECTS AGAINST ULTRAVIOLET INDUCED DAMAGE TO HUMAN SKIN Maritza A Middelkamp-Hup, MD, Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, United States, Madhu Pathak, PhD, Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, United States, Thomas Fitzpatrick, MD, PhD, Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, United States, Salvador Gonzalez, MD, PhD, Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, United States Ultraviolet radiation (UVR) induces acute epidermal and dermal damage that can lead to long-term changes such as photo-aging and skin cancer. Currently the most widely accepted method of photo-protection is the use of topical sunscreens. An oral photoprotective agent acting against UVR induced photooxidative stress would have substantial benefits over topical photo-protection in the prevention of solar UVR damage. Previous studies on Polypodium leucotomos (PL) have shown that this natural plant extract has immunomodulating and antioxidative properties. Oral administration of PL may lead to photoprotection of skin. We tested this hypothesis by exposing 10 healthy subjects of skin types II-III to varying doses of UVR from a solar simulator without PL, and 30 minutes, 1 hour (hr), 1.5 hr, 2 hrs and 3 hrs after administration of oral PL (7.5 mg/kg). Evaluation of the degree of erythema of all skin sites was performed 24 hrs later. Biopsies were obtained from skin sites exposed to the 2⫻ minimal erythema dose (MED) from PLtreated and non-treated skin after 24 or 72 hrs. Clinically, there was a significant decrease in the erythema response of skin exposed within 2 hrs after oral administration of PL (p ⬍ 0.01) when compared to PL-untreated skin. Histologically, there was a significant decrease in sunburn cells at 24 hrs (p ⬍ 0.05), DNA damage analyzed by antibodies against cyclobutane pirymidine dimers at 24 hrs (p ⬍ 0.001), proliferation visualized by Ki 67 at 72 hrs (p ⬍ 0.001), and dermal mast cell infiltration at 24 and 72 hrs (p ⬍ 0.05). In total, more than 50% of all biopsies showed Langerhans cells preservation, and this was seen in all biopsies taken at 72 hrs. Also, there was less vasodilation in PL-treated skin. In conclusion, oral PL appears to be an effective photoprotective agent by decreasing acute UVR induced skin damage such as DNA damage and Langerhans cells depletion. This short-term observation may indicate that oral PL could serve to be effective in decreasing short-term UVR damage and this may contribute to prevention of photo-induced skin cancer. S. Gonzalez is a consultant for IFC SA. 75% was supported by a Research Grant from Industrial Farmaceutica Cantabria, SA.
P136
J AM ACAD DERMATOL
P529 PHOTODYNAMIC THERAPY-INDUCED PAIN: A PATIENT CENTRED SURVEY Natasha Kapur, MBBS, The Royal Free Hospital, London, England, Kristin Kernland Lang, MBBS, University Hospital Bern, Bern, Switzerland, Lasse Braathen, University Hospital Bern, Bern, Switzerland Photodynamic Therapy (PDT) is an emerging modality in dermatology. One of its limitations is PDT-induced pain. The aim of this study was to comprehensively evaluate true discomfort induced by PDT. In a six month period, 160 patients were seen and treated with 16 37# methyl aminolaevulinic acid and illuminated with a Waldman 1200 and a fan. Prior to treatment patients received either no analgesia, paracetamol 1g or tramadol 20mg. Immediately following their treatment patients completed a questionnaire. Pain was recorded on a visual analogue scale (where 0 61# no pain and 10 61# worst pain imaginable). We evaluated the following characteristics of PDT-induced pain: (1) lesion-specific (2) site-specific (3) effect of previous PDT (4) comparison with cryotherapy (5) use and effectiveness of analgesia. The sample included 53 females and 107 males, age range 32-96 years, mean 70 years. 120 patients had actinic keratoses (AK), 29 basal cell carcinoma (BCC), 11 others including Bowens disease, squamous cell carcinoma, mycosis fungoides and epidermolysis bullosa. Mean pain score in BCC-treated patients did not differ from AK-treated patients (BCC:0.34 177#0.33 versus AK:0.28177#0.27, p61#0.43). Pain was influenced by treatment site (Head: 0.32177#0.28, Hands: 0.30177#0.30, Body: 0.22177#0.25; p60#0.05 head versus hands). Pain in patients undergoing repeat PDT did not differ from patients undergoing first PDT treatment (0.32177#0.28 versus 0.26177#0.27, p61#0.19). Of those patients who had had previous cryotherapy, 43 out of 61 patients (7037#) reported that PDT was less or equally painful. Pain scores did not significantly differ between paracetamol and tramadol treated patients (0.34177#0.26 versus 0.42177#0.29, p61#0.45). PDT is associated with a mild degree of pain, which is independent of pathology but dependent on site. Pain is not influenced by previous PDT treatment suggesting no “conditioning” effect. PDT appears at least equal or better tolerated than cryotherapy. Analgesia with paracetamol appears as effective as tramadol in 16 37# methyl aminolaevulinic acid PDT. No conflict of interests to disclose.
MARCH 2004
P528
DUAL PORPHYRIA: A CASE OF ACUTE INTERMITTENT PORPHYRIA IN ASSOCIATION WITH PORPHYRIA CUTANEA TARDA, AND A FOUR YEAR FOLLOW UP. Jason DL Williams, MBChB, Manchester University, Manchester, England, Russell Ead, MD, Manchester University, Manchester, England, Brian Kirby, MD, Manchester University, Manchester, England, Felicity Stewart, MBBS, MD, Department of Biochemistry, Hope Hospital, Manchester, England There are only four cases reported of acute intermittent porphyria (AIP) in association with porphyria cutanea tarda (PCT). Enzyme studies in these patients revealed a dual deficiency, with decreased activity of both porphobilinogen deaminase as seen in AIP and uroporphyrinogen decarboxylase, as seen in PCT. To date there have been no reports of treatment or follow up of these patients. A 48 year old lady was referred to dermatology in 1999 with a two week history of haemorrhagic blisters on the hands and feet after a holiday in Corfu. She had been diagnosed with AIP at the age of 17, having complained of abdominal pain and paraesthesia in the fingers and toes. The gene mutation causing this was subsequently identified by Professor Elder (University of Cardiff). She had had a hysterectomy at age 30 and had taken HRT since age 35. She had undergone bone marrow transplant aged 37 for acute myeloid leukaemia, and subsequently developed blisters on her feet and ears, which settled within a few weeks. She was taking Beta Blockers for hypertension. There was no family history of porphyria. Examination revealed tense non-haemorrhagic blisters on the dorsum of fingers, hands and toes. Investigations revealed elevated aminolaevulinic acid, porphobilinogen, uroporphyrin and 7-carboxyporphyrin with normal coproporphyrin. The results were consistent with a diagnosis of both porphyria cutanea tarda and acute intermittent porphyria. Plasma porphyrin screen was positive with a maximum emission at 618 nm. She has subsequently developed mild renal impairment and liver biopsy showed iron deposition. The HRT was stopped as estrogen can exacerbate both PCT and AIP, but she was unable to cope without it, because of menopausal symptoms. She was recommended oral supplements to aid weight gain and was subsequently treated unsuccessfully with hydroxychloroquine. She then underwent a course of bi-weekly venesection (total 11 units removed). This resulted in an improvement in symptoms and a marked decrease in ferritin and iron saturation levels. This case illustrates the complexity in managing patients with dual deficiency porphyrias, and reminds dermatologists of the long-term sequelae of these conditions.
CHANGES OF SKIN SURFACE TEMPERATURE INFLUENCE UV-INDUCED ACUTE HUMAN SKIN REACTION IN VIVO Oh Sang Kwon, MD, Seoul National University Hospital, Seoul, Korea, Eun Ju Hwang, MD, Seoul National University Hospital, Seoul, Korea, Seong Jin Jo, MD, Seoul National University Hospital, Seoul, Korea, Jin Ho Chung, MD, Seoul National University Hospital, Seoul, Korea Skin surface temperature at ultraviolet (UV) exposure would influence acute skin reactions such as erythema and pigmentation. Thermal changes before or after UV irradiation could influence the skin response in the way to change vascular blood flow and inflammatory response. In this study our aim was to investigate the influence of thermal changes on UV-induced acute skin reaction with relatively objective and quantitative method. Our volunteers consisted of 10 males ranging in age from 22 to 24 years with Fitzpatrick’s skin type III or IV. A sunlight fluorescent sunlamp (Waldmann UV 800) was used as a UVB light source. Either of Heat application with 45℃ heating pad or cold application with ice pack for 1 hour was done before or after UVB irradiation (control, 0.5MED, 1MED, 2MED) and then skin color was determined with Mexameter and Minolta Spectrophotometer CM-2002 for two weeks (Day 1, 3, 7, 14). The results were presented by the Erythema/Melanin indices (EI/MI) and L*a*b* system recommended by the CIE (Commission internationale de l’Eclairage). ITA (Individual Typology Angle) is also thought to be a quantitative and objective value of classifying individual skin color. In this study, compared with the only UV-exposed control, surface temperature modified groups showed generally higher Erythema Indices and a* values plus lower L*, b* values with lower UV exposure (0.5 and 1 MED). In the higher UV exposure groups of 2 MED, post-heating (UV3 Heating) and pre-cooling (Cold3 UV) groups tended to show gradually smaller MI and a* values plus higher L* and ITA values and than control in contrast to pre-heating group(Heat3 UV) and post-cooling (UV3 Cold) groups with the lower L*, ITA values and higher a* values than control. All the temperature-modified groups with any UV-irradiation showed relatively lower b* values than control. Our results indicate that alteration of the skin surface temperature modulates the degree of UV-induced acute reaction such as erythema and pigmentation. 2 MED has been suggested as the most adequate dose to assess UV-induced skin reaction in Oriental skin. In our subjects exposed to this dose, post-heating and pre-cooling showed relatively less erythema and pigmentation than other groups. These interactions between UV exposure and skin surface temperature should be considered to study the effects of natural sun exposure in routine life and to research in the field of photoprotection or UV-phototherapy.
Disclosure not available at press time.
Disclosure not available at press time.
P527 ORAL POLYPODIUM LEUCOTOMOS EXTRACT PROTECTS AGAINST ULTRAVIOLET INDUCED DAMAGE TO HUMAN SKIN Maritza A Middelkamp-Hup, MD, Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, United States, Madhu Pathak, PhD, Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, United States, Thomas Fitzpatrick, MD, PhD, Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, United States, Salvador Gonzalez, MD, PhD, Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, United States Ultraviolet radiation (UVR) induces acute epidermal and dermal damage that can lead to long-term changes such as photo-aging and skin cancer. Currently the most widely accepted method of photo-protection is the use of topical sunscreens. An oral photoprotective agent acting against UVR induced photooxidative stress would have substantial benefits over topical photo-protection in the prevention of solar UVR damage. Previous studies on Polypodium leucotomos (PL) have shown that this natural plant extract has immunomodulating and antioxidative properties. Oral administration of PL may lead to photoprotection of skin. We tested this hypothesis by exposing 10 healthy subjects of skin types II-III to varying doses of UVR from a solar simulator without PL, and 30 minutes, 1 hour (hr), 1.5 hr, 2 hrs and 3 hrs after administration of oral PL (7.5 mg/kg). Evaluation of the degree of erythema of all skin sites was performed 24 hrs later. Biopsies were obtained from skin sites exposed to the 2⫻ minimal erythema dose (MED) from PLtreated and non-treated skin after 24 or 72 hrs. Clinically, there was a significant decrease in the erythema response of skin exposed within 2 hrs after oral administration of PL (p ⬍ 0.01) when compared to PL-untreated skin. Histologically, there was a significant decrease in sunburn cells at 24 hrs (p ⬍ 0.05), DNA damage analyzed by antibodies against cyclobutane pirymidine dimers at 24 hrs (p ⬍ 0.001), proliferation visualized by Ki 67 at 72 hrs (p ⬍ 0.001), and dermal mast cell infiltration at 24 and 72 hrs (p ⬍ 0.05). In total, more than 50% of all biopsies showed Langerhans cells preservation, and this was seen in all biopsies taken at 72 hrs. Also, there was less vasodilation in PL-treated skin. In conclusion, oral PL appears to be an effective photoprotective agent by decreasing acute UVR induced skin damage such as DNA damage and Langerhans cells depletion. This short-term observation may indicate that oral PL could serve to be effective in decreasing short-term UVR damage and this may contribute to prevention of photo-induced skin cancer. S. Gonzalez is a consultant for IFC SA. 75% was supported by a Research Grant from Industrial Farmaceutica Cantabria, SA.
P136
J AM ACAD DERMATOL
P529 PHOTODYNAMIC THERAPY-INDUCED PAIN: A PATIENT CENTRED SURVEY Natasha Kapur, MBBS, The Royal Free Hospital, London, England, Kristin Kernland Lang, MBBS, University Hospital Bern, Bern, Switzerland, Lasse Braathen, University Hospital Bern, Bern, Switzerland Photodynamic Therapy (PDT) is an emerging modality in dermatology. One of its limitations is PDT-induced pain. The aim of this study was to comprehensively evaluate true discomfort induced by PDT. In a six month period, 160 patients were seen and treated with 16 37# methyl aminolaevulinic acid and illuminated with a Waldman 1200 and a fan. Prior to treatment patients received either no analgesia, paracetamol 1g or tramadol 20mg. Immediately following their treatment patients completed a questionnaire. Pain was recorded on a visual analogue scale (where 0 61# no pain and 10 61# worst pain imaginable). We evaluated the following characteristics of PDT-induced pain: (1) lesion-specific (2) site-specific (3) effect of previous PDT (4) comparison with cryotherapy (5) use and effectiveness of analgesia. The sample included 53 females and 107 males, age range 32-96 years, mean 70 years. 120 patients had actinic keratoses (AK), 29 basal cell carcinoma (BCC), 11 others including Bowens disease, squamous cell carcinoma, mycosis fungoides and epidermolysis bullosa. Mean pain score in BCC-treated patients did not differ from AK-treated patients (BCC:0.34 177#0.33 versus AK:0.28177#0.27, p61#0.43). Pain was influenced by treatment site (Head: 0.32177#0.28, Hands: 0.30177#0.30, Body: 0.22177#0.25; p60#0.05 head versus hands). Pain in patients undergoing repeat PDT did not differ from patients undergoing first PDT treatment (0.32177#0.28 versus 0.26177#0.27, p61#0.19). Of those patients who had had previous cryotherapy, 43 out of 61 patients (7037#) reported that PDT was less or equally painful. Pain scores did not significantly differ between paracetamol and tramadol treated patients (0.34177#0.26 versus 0.42177#0.29, p61#0.45). PDT is associated with a mild degree of pain, which is independent of pathology but dependent on site. Pain is not influenced by previous PDT treatment suggesting no “conditioning” effect. PDT appears at least equal or better tolerated than cryotherapy. Analgesia with paracetamol appears as effective as tramadol in 16 37# methyl aminolaevulinic acid PDT. No conflict of interests to disclose.
MARCH 2004