Primary vasculitis is classified according to vessel size in 2012 revised international Chapel Hill consensus conference nomenclature；Takayasu arteritis（TAK）and giant cell arteritis（GCA）were classified into large vessel vasculitis（LVV）and ANCA associated vasculitis（AAV）were classified as small vessel vasculitis different from immune complex related vasculitis.
LVV has been treated with glucocorticoids（GCs）and various immunosuppressants, but they are often refractory. Recently, some studies reported the efficacy of interleukin-6-receptor inhibitor, tocilizumab（TCZ）, for LVV. GiACTA study showed that the efficacy of remission maintenance in GCA patients without GCs, while TAKT study reported the efficacy of the prevention of relapse in the refractory TAK patients.
For AAV, rituximab is emerged as the alternative option to cyclophosphamide and azathioprine for remission induction and maintenance treatments. Additionally, recent report suggested GCs sparing effect of C5a receptor inhibitor, avacopan.
Stevens-Johnson syndrome（SJS）is an acute inflammatory vesiculobullous reaction of the skin and mucosa such as the ocular surface, oral cavity, and genitals. In patients with extensive skin detachment and a poor prognosis, the condition is called toxic epidermal necrolysis（TEN）. Severe ocular complications（SOC）appear in about half of SJS/TEN patients diagnosed by dermatologists. Ophthalmologists tend to report both SJS and TEN with severe ocular complications as“SJS”in a broad sense. Cold medicines, including multi-ingredient cold medications and non-steroid anti-inflammatory drugs（NSAIDs）were the main causative drugs of SJS/TEN with SOC in all SJS and TEN patients.
Cold medicine-related SJS/TEN（CM-SJS/TEN）with SOC was strongly associated with HLA-A＊02 : 06 in the Japanese populations, and significantly associated with some genes such as IKZF1 gene. As we found several HLA-SNP sets with a high odds ratio, we postulated that they may help to predict the possible development of SJS/TEN with SOC.
When the diagnosis of hair loss diseases is not definitive, trichoscopy using dermoscopy is useful for confirmation. First, the clinical hair loss pattern should be defined. When round hair loss is observed, alopecia areata is most likely, and trichoscopic features, such as black dots, broken hairs, tapering hairs, yellow dots and short vellus hairs, should be checked. In the case of patterned hair loss of the frontal and vertex scalp, hair diameter diversity（>20%）should be confirmed. Band-like hair loss suggests ophiasis-type alopecia areata or frontal fibrosing alopecia, and diffuse hair loss suggests diffuse type alopecia areata, female pattern hair loss or telogen effluvium. Therefore, trichoscopy findings support each diagnosis.
Skin changes can be significant early manifestations of collagen diseases. We discuss the clinical cases involving 5 patients who presented with skin complaints and skin changes whose final diagnoses were collagen diseases. In each case, the initial skin manifestations were important in confirming the diagnosis.
Patient 1 visited our hospital with recurrent perniosis. The physical examination revealed sclerosis of the hands and a diagnosis of systemic sclerosis was established. Patients 2 and 3 presented with intractable hand eczema. Patient 2 exhibited“mechanic’s hands”on physical examination and a diagnosis of dermatomyositis was made. The condition was resolved following surgery for renal cell carcinoma. In this case, the condition of“mechanic’s hands”was a cutaneous sign of renal malignancy. Physical examination for patient 3 revealed an inverse Gottron’s sign. A diagnosis of interstitial lung disease was made.
Patient 4 presented with recurrent pruritic skin eruptions that preceded a subsequent diagnosis of papulo-squamous-type subacute cutaneous lupus erythematosus.
Patient 5 presented with evidence of persistent angioedema on the right side of the face. A diagnosis of Sjogren syndrome was later established.
Based on the physical findings and final diagnoses in these cases, we identified the potential significance of clinical dermatology practice related to diagnosing and managing collagen diseases.
Eosinophilic fasciitis presents with wooden or plate-like hardening of the upper and lower extremities, but lacks either finger swelling or Raynaud’s phenomenon. Eosinophilic fasciitis is occasionally induced by vigorous exercise as well as trauma, leading to the hardening of the skin and limited range of movement in the joints. Also, drug-induced or paraneoplastic eosinophilic fasciitis have also been reported. An en block biopsy reveals an inflammatory infiltrate of mononuclear cells and eosinophils in the thickened fascia. Eosinophilic fasciitis is sometimes associated with several autoimmune conditions, and morphea is the most frequent skin disease. Recently, diagnostic criteria, severity classification, and clinical guidelines for eosinophilic fasciitis were proposed also in Japan. The etiology of eosinophilic fasciitis is still not fully elucidated, because this disorder is rare and animal models have not yet established. In this review, recent findings of eosinophilic fasciitis are described.
A 38-year-old male patient developed urticaria and anaphylaxis after drinking 100 ml of a taurine-containing energy drink. Skin prick test demonstrated a positive reaction to the energy drink. Therefore, we ordered all components of the energy drink. Skin prick test was negative with these components. However, the skin scratch test had a positive reaction only with synthetic taurine. He was therefore diagnosed with anaphylaxis due to synthetic taurine. Taurine is one of the most abundant free amino acids in mammalian tissue. Both a natural type and synthetic type of taurine exist. Synthetic taurine is contained in several energy drinks. Natural taurine is present in food, especially shellfish, such as oysters, squid and other seafood. After this episode, he repeatedly ate some seafood, but no adverse reactions occurred. To our knowledge, there has been only one report of synthetic taurine in an energy drink inducing anaphylaxis in Korea. We report the first case of synthetic taurine-induced anaphylaxis in Japan.
A 76-year-old woman presented with a 2-year history of a nodule on her right mandibula. She had a large nodule with pruritic erythema on her right mandibula. An otolaryngologist prescribed antibiotics under the diagnosis of cellulitis, but they were ineffective. Laboratory examination revealed a high serum IgG4 level（501 mg/dl）. On histological examination, moderate to severe lymphoplasmacytic infiltration with fibrosis was observed. X-ray examination demonstrated destruction of several distal interphalangeal and proximal interphalangeal joints in her hands. The infiltrated plasma cells were positively stained for IgG4. A diagnosis of IgG4-related disease accompanying Kimura disease-like skin eruption and rheumatoid arthritis（RA）-like abnormality was made. Oral prednisolone（30 mg/day）led to resolution of the nodule, and the dose was tapered. However, 70 days later, she suddenly died due to interstitial pneumonia. The present case demonstrated the rare complication of interstitial pneumonia, Kimura disease-like skin eruption, RA-like abnormality and interstitial pneumonia in IgG4-related disease.
An 18-year-old woman developed dyspnea and generalized urticaria necessiating emergency treatment after taking an over-the-counter medicine for a common cold. She was referred to our institute to determine the causative agent of anaphylaxis. The medicine was composed of eight ingredients, including methyl ephedrine. Each agent was examined by a prick, scratch-chamber and oral provocation test. All results were negative, except for those for methyl ephedrine. Obtaining methyl ephedrine as a single medicine is regulated. Huscode combination tablets are usually distributed as cold medicine, and those including methyl ephedrine, were examined. Dyspnea and rhinorrhea with generalized erythema were provoked 75 minutes after Huscode combination tablet administration. No symptoms were induced by the other ingredients of Huscode combination tablets. Methyl ephedrine was presumed to be the causative agent of anaphylaxis. This is the first case report of anaphylaxis due to methyl ephedrine.
A 59-year-old woman presented at a dentist with swelling on the left side of the buccal mucosa hour and a half after temporary teeth was placed. The temporary teeth was removed a few hours later, when the woman developed a fever of 37.5℃, blisters on her palate and swelling on the pharynx that made breathing difficult. Patch tests revealed positive reactions to the temporary teeth, liquid resin, polymerized resin, 2-hydroxyethyl methacrylate（2-HEMA）, ethyleneglycol dimethacrylate（EGDMA）, gold sodium thiosulfate, potassium dichromate and mercuric chloride. However, there was no reaction to methyl methacrylate（MMA）which is the main component of acrylic resin. The liquid resin includes methacrylate monomers, which have a structure similar to that of 2-HEMA and EGDMA. Based on these result, we diagnosed a methacrylate resin allergy. There are fewer reported cases of methacrylate resin allergy in dental patients than in dental workers；indeed, there are just four, including this case, possibly because it is easy to overlook mild symptoms. It was important that we included 2-HEMA and EGDMA, not just the main agent in patch testing when we suspected a methacrylate resin allergy.
Contact dermatitis due to methacrylic resin in a dental assistant A 45-year-old female presented with erythema on the 1st to 3rd fingers of her right hand, which developed after she started working as a dental assistant one month before her visit. When washing a bottle containing resin at the dental clinic, the patient had wiped the resin with the 1st to 3rd fingers of her right hand while wearing gloves. As contact dermatitis from the resin was suspected, and a patch test was conducted using a resin series, the resin polymer, and the resin monomer（each diluted to 1%）. Two of the resin series samples（ethylene glycol dimethacrylate（EGDMA）and 2-hydroxyethyl methacrylate（2-HEMA））and the resin monomer produced positive reactions. The patient was thus diagnosed with contact dermatitis. Contact dermatitis caused by low molecular weight monomers, typically produces characteristic eruptions, including erythema and swelling of the fingers. In addition, methacrylic resin can penetrate many types of gloves；therefore, care is necessary when handling it.
We report the case of 52-year-old Japanese female who was diagnosed with allergic contact dermatitis（ACD due to the temple tips of her plastic spectacle frames. The patient developed scaly infiltrative erythema on the upper parts of the bilateral pinnae after wearing the spectacles for 6 months. Patch tests produced positive results for scrapings from the temple tips but negative results for oil-soluble dyes such as C.I. Solvent Orange 60. When the temple tips were removed from the frames, their metal cores were found to be corroded. Fluorescent X-ray spectroscopy-based metal component analysis revealed that nickel was present in the temple tip resin and was one of the main components of the corroded metal cores. A patch test with nickel sulfate produced strong positive results. Some ultraviolet absorbers and plasticizers, which were detected by gas chromatography/mass spectrometry-based analysis, produced negative patch test results. We finally diagnosed the patient with nickel allergy after being sensitized to nickel, which had permeated through the metal cores of the spectacle frames after they had been corroded by sweat and sebum.
A 66-year-old woman with a previous history of atopic dermatitis came to our hospital for erythema that had developed on the left side of her neck 3 months earlier which had since spread to her face, forearm, and supraclavicular fossa. She had begun practicing the violin 18 months previously and used excessive amounts of rosin. The patch test results were positive for rosin, nickel and her own violin rosin but doubtful for the rosewood used in the chin rest. First, we changed the rosin to carbon. However, erythema remained on the left lower jaw. We also changed the rosewood to ebony and all metals（including nickel）to titanium, and her symptoms disappeared. Therefore, we made a diagnosis of allergic contact dermatitis due to rosin, nickel and rosewood in consideration of the distribution of the eruptions on her neck. She has had no recurrence after follow-up for 18 months with continued violin practice. There have been few reports regarding allergic contact dermatitis in violinists in Japan, although there have been many such reports in other countries. It is necessary to determine the causes and clinical features of allergic contact dermatitis and substitute products as necessary to resolve the symptoms.
Case 1：A 42-year-old man with edematous erythema that developed on his buttocks after 1 week of using a tribenoside-lidocaine ointment to treat external hemorrhoids was examined. Case 2：A 26-year-old woman with edematous erythema that developed on her buttocks 10 days after using a tribenoside-lidocaine ointment to treat external hemorrhoids, in whom the erythema spread to the across her entire body, was examined. Case 3：A 37-year-old woman was examined. She developed erythema on her buttocks after 2 weeks of treating external hemorrhoids using tribenoside-lidocaine ointment, and following continued ointment treatment after presentation, the eruption spread across her entire body. On patch testing, all 3 patients demonstrated allergic positive reactions to the tribenoside-lidocaine ointment and tribenoside. In case 2, we confirmed that the minimal eliciting concentration of tribenoside on patch testing was 0.01%pet.
A 64-year-old Japanese female visited our clinic after developing severe dermatitis and bullae on her fingers. She had started to make accessories using ultraviolet（UV）-cured acrylic resin a month ago, during which she wore cloth gloves or disposable polyethylene gloves. After she made the accessories the second time, she developed mild swelling, pain, and itching in her fingers, which subsided within a few days after the application of an over-the-counter ointment. After she made the accessories the third time, she developed severe hand dermatitis and visited our clinic. Patch tests using 1%, 0.5%, and 0.1% UV-cured acrylic resin and an accessory as is produced positive results on days 2, 3, 7 and 10. Further tests using several monomers of acrylic resin produced positive results for 0.1% 2-hydroxyethyl acrylate（2-HEA）on days 2, 3, 7 and 12, and doubtful reactions for 2% 2-hydroxyethyl methacrylate（2-HEMA）on days 3, 7 and 12. Tests of 1% HEMA produced negative results. As the UV-cured acrylic resin contained 2-HEA at a concentration of 0.94%, we diagnosed the patient with allergic contact dermatitis caused by 2-HEA and determined that she had become sensitized to acrylic resin within two weeks after making accessories. Resin allergies can develop when making accessories as well as during dental treatment or when wearing artificial nails or cosmetics. It is necessary to be aware that patients should not touch acrylic resin with their bare hands or when wearing disposable gloves; i.e., disposable gloves are insufficient for protecting against sensitization to acrylic resin.