A case of IgA vasculitis with necrotizing arteritis in a 13-year-old girl.

IgA vasculitis (IgAV) is the most frequent form of vasculitis in childhood which classically presents with purpura of the lower extremities, joint pain or swelling and abdominal pain. Though it is a self-limiting disease, and its prognosis is generally good, glomerulonephritis is one of the most important complications. IgAV is classified as a small vessel vasculitis, and though glomerulonephritis develops in IgAV, necrotizing arteritis is rarely seen. Here, we present a case of a 13-year-old girl with IgAV, glomerulonephritis, and necrotizing arteritis in the small renal arteries. There have been only a few reports of adult cases of IgAV with necrotizing arteritis in the kidneys, but there have been no pediatric cases. Some previous reports showed a high mortality rate and implied the possibility of overlap with other vasculitides. In the current report, a rare case of IgAV is described which exhibited necrotizing arteritis rather than overlap with another vasculitis, with a relatively typical clinical course for IgAV and laboratory tests.

Contact Dermatitis Caused by Efinaconazole and Luliconazole.

We report a case of contact dermatitis caused by both efinaconazole, a topical triazole antifungal drug, and luliconazole, a topical imidazole antifungal drug. Positive patch test reactions were observed with efinaconazole and luliconazole. A patch test with lanoconazole also elicited a positive reaction. We hypothesized that structural similarity between luliconazole and lanoconazole led to cross-reaction, and that the dithiolane ring common to both drugs or the structure of the vinyl imidazole with a dithiolane ring could be the antigenic determinant. Since efinaconazole and luliconazole have no common structures, patients could be sensitized to both drugs separately. The antigenic determinant of efinaconazole is unknown. However, the chemical formula of ravuconazole, an oral triazole antifungal drug, is similar to that of efinaconazole. Clinicians should carefully consider potential cross-reactivity between these drugs.

A synonymous splice site mutation in IL2RG gene causes late-onset combined immunodeficiency.

X-Linked severe combined immunodeficiency (X-SCID) is a severe form of primary immunodeficiency characterized by absence of T cells and NK cells. X-SCID is caused by a loss-of-function mutation in the IL2RG gene that encodes common gamma chain (γc), which plays an essential role in lymphocyte development. We report the first case of hypomorphic X-SCID caused by a synonymous mutation in the IL2RG gene leading to a splice anomaly, in a family including two patients with diffuse cutaneous warts, recurrent molluscum contagiosum, and mild respiratory infections. The mutation caused aberrant splicing of IL2RG mRNA, subsequently resulted in reduced γc expression. The leaky production of normally spliced IL2RG mRNA produced undamaged protein; thus, T cells and NK cells were generated in the patients. Functional assays of the patients' T cells and NK cells revealed diminished cytokine response in the T cells and absent cytokine response in the NK cells. In addition, the TCR repertoire in these patients was limited. These data suggest that a fine balance between aberrant splicing and leaky production of normally spliced IL2RG mRNA resulted in late-onset combined immunodeficiency in these patients.

Two Cases of Verrucous Carcinoma: Revisiting the Definition.

Verrucous carcinoma (VC) is an uncommon, distinct type of well-differentiated squamous cell carcinoma. Here we present two cases of VC, one arising from the lower leg and the other from genital skin. Case 1, a female patient, aged 95 years, had a brownish verrucous plaque on her right lower leg. Histopathologically, epithelial tumor cells grew pushing the stroma, while the basement membrane was intact. No prominent cellular atypia or hyperchromatin was found. Case 2, a male patient, aged 53 years, had a verrucous plaque at the border between his scrotum and inner aspect of his thigh. A pathological diagnosis of VC was made using an excisional specimen. Making a definitive diagnosis of VC is challenging but crucial. Pathological diagnosis using a small specimen might cause underdiagnosis or overdiagnosis. To avoid this, pertinent pathological diagnosis using an ample specimen is required. We also revisited the definition of VC to precisely understand its nature.

Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?

Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections.

Hashimoto's thyroiditis with clinical manifestations resembling dermatomyositis: a case report.

We report on a 59-year-old man with a 1-year history of forearm erythema, bilateral limb arthralgia, and muscle weakness. During the initial examination we observed infiltrative erythema of the forearm and muscle weakness and atrophy of the limbs. Blood tests revealed marked increases in myogenic enzymes. Because histopathological studies showed lymphocytic infiltration around the small blood vessels in the dermis and mucin deposition, we made a tentative diagnosis of dermatomyositis. However, the specific cutaneous manifestations of dermatomyositis, including heliotrope erythema and Gottron's sign, were absent, and the findings of electromyography were normal. A subsequent detailed examination revealed hypothyroidism and high titers of antithyroglobulin and antimicrosome antibodies, and we made a definitive diagnosis of Hashimoto's thyroiditis. The thyroid function and skin manifestations both improved after treatment with levothyroxine sodium. Dermatomyositis and Hashimoto's thyroiditis can exhibit similar characteristics, and caution is required because of the possibility of misdiagnosis.

IgA vasculitis complicated by cytomegalovirus enteritis: a case report.

A 61-year-old man was admitted to our department with purpura and hemorrhagic bullae on his lower limbs, dull pain affecting the entire abdomen, and hematochezia. Histopathological examination and immunostaining revealed leukocytoclastic vasculitis of the small blood vessels of the dermis and IgA deposition; multiple ulcers were observed in the ileum during lower gastrointestinal (GI) endoscopy, so we made a diagnosis of IgA vasculitis (Henoch-Schönlein). Treatment with oral prednisolone (PSL) at a dose of 80 mg/day (1 mg/kg/day) for one week resolved the symptoms almost completely. However, when the PSL dose was later reduced, dull epigastric pain and discomfort flared up again. Multiple punched-out ulcers were observed in the duodenum during upper GI endoscopy, and immunostaining revealed cytomegalovirus (CMV) in vascular endothelial cells and infiltrating cells. The patient's serum was positive for CMV antigenemia. On the basis of these findings, we concluded that the CMV enteritis had developed as a complication arising from the patient's immunosuppressed state, which was itself a result of the steroid therapy. We treated the patient with ganciclovir, which relieved the abdominal symptoms.

E-cadherin interactions are required for Langerhans cell differentiation.

Human skin contains the following two distinct DC subsets: (i) Langerhans cells (LCs), expressing Langerin but not DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), are predominantly localized in the epidermis; and (ii) dermal DCs, expressing DC-SIGN but not Langerin, are observed mainly in the dermis. It is not known whether localization in the epidermis provides cues for LC differentiation. Here, we show that E-cadherin expressed by epidermal keratinocytes (KCs) is crucial for differentiation of LCs. Monocytes differentiated into LC-like cells in presence of IL-4, GM-CSF, and TGF-ß1. However, these LC-like cells expressed not only Langerin but also DC-SIGN. Notably, co-culturing of these LC-like cells with KCs expressing E-cadherin or recombinant E-cadherin strongly decreased expression of DC-SIGN and further induced a phenotype similar to purified epidermal LCs. Moreover, pretreatment of LC-like cells with anti-E-cadherin-specific antibody completely abolished their Langerin expression, indicating the requirement of E-cadherin-E-cadherin interactions for the differentiation into Langerin(+) cells. These findings suggest that E-cadherin expressed by KCs provide environmental cues that induce differentiation of LCs in the epidermis.