Atsushi Hatamochi

Successful treatment of granulomatous cheilitis with roxithromycin

Dear Editor, A 13-year-old boy visited our department on 14 May 2005 with the chief complaint of swelling of the lower lip, which had begun to develop approximately 1.5 years previously in the absence of any particular provoking factors. Initial clinical examination showed swelling of the entire lip area, including the lower lip (Fig. 1a). The patient had no subjective symptoms, including itching, and no evidence of facial nerve paralysis or a lingua plicata was recognized. A plain chest roentgenogram taken during a routine school health examination revealed no abnormalities. Although he had a past history of dental treatment, no carious teeth were recognized at the initial examination, and no metal crown had been used in the dental treatment. Laboratory examination revealed no hematological or biochemical abnormalities. The serum level of immunoglobulin E, which seemed to be associated with allergic rhinitis, was elevated to 1490 mg/dL. Histopathological findings in biopsy specimens of the swollen lips showed partial thickening of the epithelium, edema and vasodilation in the upper layer of the dermis. Infiltration by small round cells and granulomatous lesions were recognized in the middle and lower layers of the dermis (Fig. 2). Therefore, a diagnosis was made of granulomatous cheilitis. On 14 June 2006, the patient was started on oral minocycline at a dose of 100 mg/day, and the drug was continued for 45 days. Because no change in the condition of the lips was noted, oral azithromycin was begun at a dose of 1500 mg/week and administrated for another 10 weeks, however, the patient’s condition remained unresponsive to treatment. Subsequently, the patient was started on oral roxithromycin at a dose of 150 mg/day; with this treatment, the swollen lips began to improve gradually by 2 months after the drug was started, and subsided almost completely by 5 months after the start of the treatment (Fig. 1b). At present, approximately 6 months after the discontinuation of roxithromycin, there has been no relapse.

Characterization of a New Syndrome That Associates Craniosynostosis, Delayed Fontanel Closure, Parietal Foramina, Imperforate Anus, and Skin Eruption: CDAGS

We describe the clinical characterization, molecular analyses, and genetic mapping of a distinct genetic condition characterized by craniosynostosis, delayed closure of the fontanel, cranial defects, clavicular hypoplasia, anal and genitourinary malformations, and skin eruption. We have identified seven patients with this phenotype in four families from different geographic regions and ethnic backgrounds. This is an autosomal recessive condition that brings together apparently opposing pathophysiologic and developmental processes, including accelerated suture closure and delayed ossification. Selected candidate genes--including RUNX2, CBFB, MSX2, ALX4, TWIST1, and RECQL4--were screened for mutations, by direct sequencing of their coding regions, and for microdeletions, by fluorescent in situ hybridization. No mutations or microdeletions were detected in any of the genes analyzed. A genomewide screen yielded the maximum estimated LOD score of +2.38 for markers D22S283 and D22S274 on chromosome 22q12-q13. We hypothesize that the gene defect in this condition causes novel context-dependent dysregulation of multiple signaling pathways, including RUNX2, during osteoblast differentiation and craniofacial morphogenesis.

A Case of Angiolymphoid Hyperplasia with Eosinophilia (ALHE) of the Upper Lip

Angiolymphoid hyperplasia with eosinophilia (ALHE) is clinically characterized by intradermal or subcutaneous papules and/or nodules usually occurring in young adults. Lesions in the oral mucosa are extremely rare. We report a case and review the literature of ALHE cases involving the oral mucosa. A 40‐year‐old man presented with a painless, 20 × 20 mm, submucosal nodule on the upper lip. Histological examination of lip biopsy specimens revealed an increase in many small vessels. The vascular walls consisted of prominent endothelial cells with a histiocytoid appearance, which protruded into the lumen. Many eosinophils and lymphocytes were also seen around the vessels. The diagnosis of ALHE was made from the above findings.

Ichthyosiform Mycosis fungoides: Report of a Case Associated with IgA Nephropathy

We report a case of ichthyosiform mycosis fungoides (MF) associated with IgA nephropathy. Histological examination showed a dense atypical lymphocytic infiltrate admixed with epithelioid cells and giant cells in the dermis associated with the features of epidermotropism and folliculotropism. Reported cases of ichthyosiform MF are reviewed and histopathological characters of ichthyosiform MF are summarized. We suggest a histiocyte/dendritic-cell-rich infiltrate, or granulomatous features of infiltrate may be another characteristic of ichthyosiform MF. This case was associated with IgA nephropathy, which is uncommon. Such a presentation has never been reported in the literature.

Association between eosinophilic fasciitis and systemic lupus erythematosus

Dear Editor, Since the first description of eosinophilic fasciitis (EF) by Shulman in 1974, numerous reports of this condition have been published, establishing it as an entity different from scleroderma. The characterization of EF has broadened with increasing reports of unusual manifestations and disease associations suggesting possible overlap with other collagen disorders. EF has been reported in association with morphea, systemic sclerosis, Sjögren’s syndrome and antiphospholipid antibody syndrome. However, to the best of our knowledge, only four cases of EF in association with systemic lupus erythematosus (SLE) have been published. We describe here a patient with systemic lupus erythematosus who developed EF. A 25-year-old woman with a 15-year history of Raynaud’s phenomenon and 3-year history of a butterfly rash on the face, alopecia and photosensitivity, presented in August 2004 with an 8-month history of symmetrical subcutaneous indurations on both arms. Before the appearance of these subcutaneous indurations on the arms, the patient used to play tennis. She also complained of symmetrical pain of the proximal interphalangeal and metacarpophalangeal joints, elbows and knees. On examination, the patient was found to have marked subcutaneous sclerosis on the inner and extensor aspect of both the upper arms (Fig. 1) and flexor aspect of both lower arms. Livedo racemosa was observed extending from the elbow to the extensor aspect of both the lower arms. Laboratory evaluation revealed a hematocrit value of 33%, hemoglobin level of 14.4 g/dL, red blood cell count of 333 × 10/mm and white blood cell count of 3600/mm, with 5% eosinophils. The serum creatinine level was normal. Serum γ-globulin was 21% (10.4–20.1%). The serum level of C3 was decreased and that of C4 was at the lower limit of the normal range. The serum was positive for antinuclear antibodies at a titer of 1:640, with a homogeneous pattern. Tests for anti-single-stranded-DNA antibody and anti-double-stranded DNA antibody were also positive. A biopsy specimen including the fascia and muscle obtained from the right upper arm showed prominent thickening of the fascia due to fibrosis, with an inflammatory mononuclear cell infiltrate. Thickening of the collagen bundles was observed, occasionally extending to the septa of the subcutaneous fatty layer and deep reticular layer of the dermis (Fig. 2a,b). Treatment with oral prednisolone (30 mg/day) was started, and within 1 month, the induration on the patient’s arms decreased and the patient no longer complained of joint pains. The dose of prednisolone was tapered and, at present, the patient, receiving low-dose steroid therapy (5 mg/day), remains asymptomatic and the white blood cell count, serum level of C3 and serum γ-globulin value are normalized; however, the titers of antinuclear antibodies and anti-doublestranded DNA antibody are almost unchanged. Our patient showed malar rash (butterfly-shaped erythematous rash on the face), photosensitivity,

A case of sarcoidosis with livedo

A 35-year-old woman presented to our department in the end of May 2006 with a chief complaint of misty vision and dysphagia since February, and reticular purplish erythema on both legs from early May. Her family history and past history were unremarkable. Physical examination revealed reticular purplish erythema, i.e. livedo, on both legs (Fig. 1). There were no subjective symptoms, such as itching. Laboratory investigations revealed no abnormalities of the blood count, electrolyte panel, or renal and liver function tests. The serum levels of angiotensin II-converting enzyme (30.2 IU/L; normal, 7.0–25.0 IU/L) and lysozyme (17.3 lg/mL; normal, 4.2–11.5 lg/mL) were elevated. Repeated testing for antinuclear antibody revealed the presence of this antibody at a titer of 1 : 160 (homogeneous and speckled pattern). Antinuclear antibody screening for specific antibodies (including antibodies to SSA/Ro, SSB/La, SM, and Ul-snRNP) was negative. Serum test for antiphospholipid antibody was negative. The bleeding time was normal and there were no abnormalities of the blood coagulation profile. A sputum culture for tubercule bacilli was negative. The tuberculin test was negative. There were no abnormal electrocardiogram (ECG) findings. Magnetic resonance imaging (MRI) and magnetic resonance angiography of the head showed no evidence of tumor or vascular lesions. Plain roentgenography and computed tomography (CT) of the chest revealed bilateral hilar lymphadenopathy (BHL). Transbronchial lung biopsy revealed the presence of epithelioid cell granulomas in the lung tissue. Ophthalmologic examination revealed bilateral iritis, trabecular nodules, and keratitic precipitates, and fluorescein angiography of the fundus revealed vascular lesions of the ocular fundus. 1217 Figure 1 Reticular purplish erythema of both legs

A case of confluent and reticulated papillomatosis that successfully responded to roxithromycin

Dear Editor, Confluent and reticulated papillomatosis (CRP), characterized by the development of a fine network of pigmented maculae on the chest, between the shoulder blades and on other areas of the trunk, was first described by Gougerot and Garteaud in 1927.1 The etiology of CRP remains unclear; accordingly, there is no standard therapy. Various treatments have been tried, and there have been some reports of CRP responding to minocycline in recent years.2 Herein, we report a patient with CRP who failed to respond to minocycline, although roxithromycin proved very effective. A 28-year-old Japanese man had a 6-month history of reticular pigmented maculae on the lower abdomen, trunk and arms. On examination, he had brown reticular maculae with relatively clear borders on both flanks, as well as extending from the lower abdomen to the outer sides of the thighs, from the axillae to the shoulder blades, and on the back. Scales were also present in some areas (Fig. 1). Physical examination showed that the patient was 169 cm tall, weighed 56 kg, and had a body mass index of 19.6%; he was not obese. Histopathological examination of skin biopsy specimens from the flanks revealed papillomatosis of the epidermis and slight hyperkeratosis (Fig. 2). The basal layer showed a slight increase of melanin in some areas. No changes were observed in the dermis or subcutaneous fatty tissue. Periodic acid-Schiff (PAS) staining did not detect fungal elements. Blood tests found no abnormalities in the cell count or fasting blood glucose (96 mg/dL). Scales were sampled from the trunk, but microscopy found no evidence of Malassezia furfur or other fungi. On the basis of the clinical and histopathological findings, a diagnosis of confluent and reticulated papillomatosis (CRP) was made. The patient was then started on oral minocycline (200 mg/day). However, no improvement of the lesions was evident after 3 months. The antibiotic was thus changed to oral roxithromycin (300 mg/day). After 1 month on this regimen, the rash had improved to slight pigmentation, and it then almost completely disappeared in the next month (Fig. 3a,b).

Syringocystadenoma papilliferum associated with apocrine poroma

A 65‐year‐old Japanese man presented with a gradually enlarging mass on the right side of the abdomen, which he had first noticed about 4 years previously. He was otherwise asymptomatic. Histopathological examination of the mass revealed an aggregation of neoplastic cells (tumor cell nests) with cellular proliferation extending from the epidermis to the dermis. The tumor consisted of two histologically distinct parts. One part was composed of uniformly small cells with a cuboidal appearance. Some ductal structures were visualized, and some of the cells lining the ductal lumina contained decapitation secretions. These histological changes were consistent with the diagnosis of apocrine poroma. The remaining part of the tumor was composed of cystic invaginations with numerous projections oriented toward the lumen. There were two rows of cells in the projections; the cells on the luminal side were columnar, and those at the apical aspect were small cuboidal cells. These histological changes were characteristic of syringocystadenoma papilliferum (SCAP). Based on these findings, a diagnosis of SCAP associated with apocrine poroma was made. To the best of our knowledge, there have been no previous reports of such a case in the published work.

A case of cutaneous leiomyosarcoma with overexpression of KIT: do CD117 (KIT)-positive primary gastrointestinal stromal tumours of the skin exist?

have been withdrawn in the U.K. and U.S.A. because they were associated with life-threatening arrhythmias in susceptible individuals. Concerns of cardiac toxicity of other NSAs have not been substantiated from numerous clinical and pharmacosurveillance studies, even at high dosages, such as six times the recommended dosage of cetirizine (60 mg day) and nine times the recommended dosage of desloratidine (45 mg day). However, a single case report associated fexofenadine with harmful arrhythmogenicity, although the patient did have pre-existing cardiac morbidity. The risks of sedation are much lower compared with sedating (first-generation) antihistamines, such as chlorphenamine and hydroxyzine, because of their relative inability to cross the blood–brain barrier. Although the risk of sedation has been shown to be dose-related for cetirizine, it has been reported to be well tolerated four times above standard doses (40 mg day). Fexofenadine did not demonstrate sedation even at a dose of more than seven times the recommended dose (690 mg, twice daily). However, patients do develop tolerance to this complication. Despite this, patients should be warned about this possible adverse event, especially when the dose is increased. Urticaria can resolve spontaneously, which makes it difficult to assess completely the effectiveness of a treatment. The data on the duration of this disease are limited and are mostly derived from patients who have been referred for specialist management. In a study performed over 30 years ago, prior to the availability of antihistamines, it was shown that 50% of patients referred to a tertiary centre with urticaria alone had complete resolution of their disease after 6 months. The severity of CIU can also fluctuate and treatment should correspond accordingly. The wide therapeutic index and fast onset of action of NSAs makes them suitable for this purpose. Furthermore, there is no restriction on the duration of the use of NSAs as they are unlikely to have a cumulative side-effect profile. These features cannot be applied to systemic immunomodulatory drugs such as systemic corticosteroids and ciclosporin. There are numerous therapies to manage severe CIU. Highdose NSAs may be useful, especially when the disease has been unresponsive to lower doses. A gradual dosage titration of an NSA may be a better alternative to changing to another antihistamine or an immunodulatory agent. A combination of two or more antihistamines may also be another worthwhile course of action. Well-designed, blinded placebo-controlled studies of high-dose NSAs in severe CIU may provide better evidence of its efficacy and toxicity.

Discoid lupus erythematosus exacerbated by contact dermatitis caused by use of squaric acid dibutylester for topical immunotherapy in a patient with alopecia areata

A 57‐year‐old Japanese male patient with an 18‐year history of discoid lupus erythematosus (DLE) presented with alopecia on his scalp, and was clinically diagnosed to have alopecia areata. He was started on topical immunotherapy with squaric acid dibutylester (SADBE) for the treatment of alopecia areata. The patient was first sensitized with the application of 2% SADBE on the right upper arm, followed subsequently by re‐exposure to a low concentration of SADBE to provoke contact dermatitis on the scalp as treatment. Approximately 2 months later, he developed multiple red scaly lesions on his scalp and face, which were diagnosed histopathologically as DLE. DLE is known to be exacerbated by a variety of factors, including sunlight, X‐rays, tattoos, burns, and some forms of cutaneous trauma, including dermatitis. However, to the best of our knowledge, there have only been two reported cases of DLE exacerbated by contact dermatitis.