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Advances in dermatology and venereology Acta Dermato-Venereologica
Late-onset Erythropoietic Protoporphyria Associated with Myelodysplastic Syndrome Treated with Azacitidine
Ai YOSHIOKA 1, Susumu FUJIWARA 1, Hiroki KAWANO 2, Hajime NAKANO 3, Shigeru TAKETANI 4, Toshimitsu MATSUI 5, Yoshio KATAYAMA 2 and Chikako NISHIGORI 1
1
Division of Dermatology, 2 Division of Hematology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 6500017 5-2, Kusunoki-cho7, Chuo-ku, Kobe-shi, Hyougo, Kobe, 3 Department of Dermatology, Hirosaki University Graduate School of Medicine, Hirosaki, 4 Department of Microbiology, Kansai Medical University, Hirakata, and 5 Department of Haematology, Nishiwaki Municipal Hospital, Nishiwaki, Japan. E-mail: aiichi39 @ gmail. com Accepted Oct 19, 2017; Epub ahead of print Oct 23, 2017
Erythropoietic protoporphyria( EPP) is an inherited disorder caused by partial deficiency of ferrochelatase( FECH), the last enzyme in the heme biosynthetic pathway. The main clinical symptoms are oedematous erythema or blisters with itching and pain after exposure to sunlight, and liver dysfunction due to erythrocytolysis and accumulation of porphyrin. Erythropoietic protoporphyria is generally diagnosed during childhood; however, some adult-onset cases secondary to myelodysplastic syndrome( MDS) have been reported. Acquired EPP can develop in an individual with the occurrence of a chromosome abnormality in the FECH due to myelodysplastic syndrome, which results in reduced expression of ferrochelatase. In the case described here, the methyltransferase inhibitor, azacitidine( AZA), suppressed progression of MDS as well as the symptoms of photosensitivity, indicating that it may be effective in reversing FECH gene silencing.
CASE REPORT
A 78-year-old man visited our hospital with pain and swelling of his hands and face due to sun exposure since 4 months earlier. He had been treated with an oral angiotensin II receptor blocker, telmisartan, for high blood pressure until 1 year before the hospital visit. He initially exhibited oedematous changes on the dorsa of both hands, with lichenification extending from the dorsa to the forearms and greyish-red oedematous changes on the dorsum of the right hand( Fig. 1a). Diffuse faint erythema was observed on the dorsum of the nose and the interior of the nasolabial fold( Fig. 1b). Using a slide projector equipped with a 250-W halogen lamp illuminating at wavelengths of between 380 and 780 nm and situated 15 cm away from the patient’ s back, a poorly demarcated, non-pruriginous, erythematous macule appeared after 15 min irradiation. The patient’ s skin phototype was type IV, based on the classification by Thomas B. Fitzpatrick,
Blood examination showed moderate macrocytic anaemia( red blood cell( RBC) count 2.6 million /µ l( normal 4.3 – 5.7); haemoglobin( Hb) level 9.1 g / dl( 13.5 – 17.5); haematocrit 27.6 %( 34.8 – 25.0); mean corpuscular volume 106 fL( 80 – 100); mean corpuscular Hb level 35 pg( 30 – 35); and mean corpuscular Hb concentration 33 %( 30 – 35)). Biochemical examination showed increased protoporphyrin RBC levels( 1,341 µ g / dl, normal 30 – 86) and normal liver function. Urinalysis was normal. Histopathological examination with haematoxylin – eosin staining of skin biopsies from the dorsa of the right hand showed basal pigmentation, with periodic acid-Schiff-positive eosinophilic amorphous depositions around vessels in the upper dermis( Fig. 1c, d). Acquired EPP was suspected on the basis of the late onset of symptoms and moderate macrocytic anaemia.
Bone marrow examination showed normoplastic marrow and erythroid hyperplasia with dysplastic features.
G-banding and spectral karyotyping of the marrow cells showed an abnormality in the chromosome 18q21 in which the FECH gene resides( Fig. S1a 1). The patient’ s symptoms were consistent with refractory anaemia with ring sideroblasts because bone marrow examination showed erythroid dysplasia, the ratio of ringed sideroblasts was 26 %, and blood examination showed anaemia at his first visit only.
The FECH activity in the peripheral lymphocytes of the patient was
Fig. 1. Clinical images and histopathological findings.( a) Obvious lichenification is seen from the dorsa of both hands to the forearms as well as oedematous and erythematous changes.( b) Skin on the patient’ s face shows diffuse erythema on the dorsum of the nose / nasolabial fold.( c) Haematoxylin-eosin stain( magnification × 160): Hyperpigmentation is seen in the basal epidermal layer. Amorphous eosinophilic material is deposited around the vessels in the papillary and lower layers of the dermis.( d) Periodic acid-Schiff( PAS) stain( magnification × 320): PAS-positive tissue with deposits of amorphous material. Permission is given by the patient to publish these photos.
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2829 Acta Derm Venereol 2018; 98: 275 – 277