Yukiko Tsuji-Abe

Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer

Harlequin ichthyosis (HI) is a devastating skin disorder with an unknown underlying cause. Abnormal keratinocyte lamellar granules (LGs) are a hallmark of HI skin. ABCA12 is a member of the ATP-binding cassette transporter family, and members of the ABCA subfamily are known to have closely related functions as lipid transporters. ABCA3 is involved in lipid secretion via LGs from alveolar type II cells, and missense mutations in ABCA12 have been reported to cause lamellar ichthyosis type 2, a milder form of ichthyosis. Therefore, we hypothesized that HI might be caused by mutations that lead to serious ABCA12 defects. We identify 5 distinct ABCA12 mutations, either in a compound heterozygous or homozygous state, in patients from 4 HI families. All the mutations resulted in truncation or deletion of highly conserved regions of ABCA12. Immunoelectron microscopy revealed that ABCA12 localized to LGs in normal epidermal keratinocytes. We confirmed that ABCA12 defects cause congested lipid secretion in cultured HI keratinocytes and succeeded in obtaining the recovery of LG lipid secretion after corrective gene transfer of ABCA12. We concluded that ABCA12 works as an epidermal keratinocyte lipid transporter and that defective ABCA12 results in a loss of the skin lipid barrier, leading to HI. Our findings not only allow DNA-based early prenatal diagnosis but also suggest the possibility of gene therapy for HI.

Bacterial infection-induced generalized Hailey–Hailey disease successfully treated by etretinate

Hailey–Hailey disease (HHD; familial benign chronic pemphigus) is a hereditary blistering disorder characterized by episodic maceration and erosions mainly in intertriginous areas, and generalized eruptions are rarely seen. We report here a 51‐year‐old woman with generalized HHD who was successfully treated with oral etretinate. The present case suggests that oral etretinate is effective against the generalized eruptions even in cases in which bacterial infection has triggered the generalization of HHD.

Aggressive squamous cell carcinoma developing in a giant epidermal cyst of the abdomen

Mono-letter mnemonics in dermatology A mnemonic is a device or code that helps an individual to memorize key information about something. Many people are using mnemonics in teaching as they have been proven to be a successful learning aid. Recently, we have reviewed the use of mnemonics in dermatologic disorders. Many websites and books compile lists of mnemonics; thus, there may be more than one mnemonic for a given disorder. It is left to the individual to select one that he or she prefers. It is not uncommon for individuals to devise their own methods of remembering facts by constructing a word, song, picture, or incident. Self-made mnemonics are often particularly effective, as the time and creative energy devoted to their development result in increased recall. We wish to point out in this brief communication that using a word or phrase for mnemonics may at times become outdated, similar to a new edition of a book which replaces a previous one. Mnemonics, too, must accommodate new information so that students can reap the maximum benefit from this useful learning aid. Problems can arise when new information is added, because the addition of a letter to the existing word or phrase will ultimately change the composition of a mnemonic that has been in vogue for some time. For instance, the five painful tumors of the skin have been grouped nicely into the word “Bengal” (blue rubber bleb nevus, eccrine spiradenoma, neurilemmoma/neuroma, glomus tumor, angiolipoma/angioleiomyoma/angiosarcoma, and leiomyoma), or the phrase “blend an egg”, but now, with the potential addition of cutaneous endometriosis/calcinosis cutis and osteoma cutis, its use may be rendered obsolete. The new mnemonic for painful cutaneous nodules is BENGAL CO, where “CO” refers to the first letter of the last two tumors mentioned. In addition, a word or phrase that may be of interest to individuals in some countries, and easily recalled by them, might not be of interest elsewhere or may be difficult for persons in other places to recall. We wish to highlight that one good technique that can be used in framing mnemonics is a mono-letter. With this technique, it is possible to avoid the unnecessary inclusion of letters that change the meaning of the word, it can be used globally and internationally, and it is easily remembered because of its acceptability. This has been welcomed by other specialties. The letters may be employed in independent words or in words contained in a large statement. An example of the latter is the memorable description of Dowling–Degos disease by Wilson-Jones and Grice: demonstrating dusky dappled disfigurements and dark dot depressions, and disclosing digitate downgrowths delving dermally. Here, we list some of the “mono-letter” mnemonics that can be used as an aid in teaching dermatology: “a” in Addison’s disease [asthenia, areola pigmentation, arterial hypotension, alimentary abnormality (anorexia, symptoms of acute abdomen), anxiety, axillary and pubic hair thinning]; “d” and “m” in pellagra [dementia, diarrhea, dermatitis, death, meats (mostly fats), molasses, meal (corn)]; “l” in a dermatopathology pattern with superficial and deep perivascular infiltrates with lymphocytes predominant [ light eruption (polymorphus), lupus erythematosus, lymphocytic infiltrate of Jessner + deep figurate/gyrate erythema, Lyme disease, lues (syphilis) (+ plasma cells), lymphoma, leukemia, leprosy, indeterminate type (+ histiocytes)]; “p” in telogen effluvium (pregnancy, protein depletion, pills, propranolol, pyrexia, parturition, psychic stress); “p” in lichen planus (purple, polygonal, planar or flat, papules, pruritic, persistent, penile); “s” in superficial chronic glossitis [smoking, spirit (alcohol), spices, syphilis, sharp objects (trauma), sepsis (chronic debilitating diseases)].

Cutaneous pemphigus vulgaris with skin features similar to the classic mucocutaneous type: a case report and review of the literature.

Pemphigus vulgaris (PV) is a life‐threatening autoimmune blistering skin disease that specifically involves oral mucosa. It was recently shown that a very small number of patients with PV show no mucous membrane involvement although they have circulating autoantibodies directed against both desmoglein (Dsg)1 and Dsg3 that are associated with histopathological suprabasal acantholysis. These cases are classed as cutaneous‐type PV. We report here a case of cutaneous‐type PV that occurred in a 50‐year‐old man. Clinical examination revealed numerous tense and spreading blisters and erosions over the patient’s entire body, similar to the classic mucocutaneous‐type PV. Interestingly, none of the previously reported patients with cutaneous PV had shown skin features like those of mucocutaneous PV, whereas the present case clearly demonstrated very typical clinical features similar to those in mucocutaneous PV.

A severe and refractory case of anti-p200 pemphigoid resulting in multiple skin ulcers and scar formation.

Anti-p200 pemphigoid is a recently described autoimmune blistering skin disease that is characterized by the presence of autoantibodies against an unidentified 200-kDa dermal autoantigen. Most of the previous cases have been successfully treated using mild-to-moderate immunosuppressive therapies, which resulted in a good prognosis. We report here a severe and refractory case of anti-p200 pemphigoid that developed in a 53-year-old woman, in which blisters led to multiple skin ulcers, followed by severe scar formation. In the present case, methylprednisolone pulse therapy was effective enough to reduce the disease activity.

Tumour-like muscular sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown aetiology with variable manifestations, which may affect virtually any organ. Muscular sarcoidosis is a rare entity, and among this group of muscular lesions, the tumour‐like muscular sarcoidosis subtype is extremely rare. We report on two sarcoidosis cases that presented muscular sarcoid lesions with subcutaneous tumours.

Epidermodysplasia verruciformis and generalized verrucosis: the same disease?

We report a patient with epidermodysplasia verruciformis (EV) who had severe generalized verrucous skin lesions for 50 years without any immunological abnormality. Microscopic examination showed two histopathological features, including seborrhoeic keratosis and common warts. The detected human papilloma virus (HPV) types were found to be HPV 3, 50, 5, and 76, using a degenerate PCR method. EV and generalized verrucosis are distinguished by slight differences in clinical symptoms or HPV types, so there should be no apparent differential points common to both diseases. Therefore, we propose that an abnormal susceptibility specific to HPV, which is the most characteristic feature in EV, should be regarded as a differential point in these two diseases.

Acquired perforating dermatosis appearing as elastosis perforans serpiginosa and perforating folliculitis

associated with inflammatory lesions. In these cases the lesions were located on the trunk, where the acne lesions were found. Other retinoids such as etretinate and topical retinoids, have also been associated with PG-like lesions. In addition to retinoids, PG-like lesions have been reported with indinavir treatment, an inhibitor of a human immunodeficiency virus (HIV)-1 protease, in up to 5.9% of patients. In these cases the lesions are distributed in the lateral nail folds, most commonly in the toes. It is believed that in this specific location, the disorder is trauma-related. Some homologies between the amino-acid sequences of retinoid acid-binding protein and the catalytic site of HIV-1 protease may explain the cutaneous side-effects of these two drugs. However, the pathogenic mechanism remains unknown. The only previous report of PG-like lesions related to capecitabine treatment was described by Piguet et al. The patient received capecitabine for 4 months and developed lesions in eight of his toes. The lesions resolved 1 month after discontinuation of capecitabine. Although there are some reports describing onycholysis in relation to capecitabine, no further reports of PG-like lesions have been described. Whether there are some similarities between capecitabine and retinoids or indinavir is not known. Dermatologists should be aware of the common cutaneous side-effects of capecitabine, including PG-like lesions.