The cause of fibrotic diseases, pathologies characterized by excessive production, deposition, and contraction of extracellular matrix, is unknown. To understand the molecular basis of fibrotic disease, it is essential to appreciate how matrix deposition is normally controlled and how this process is dysregulated in fibrogenesis. This review discusses the current state of knowledge concerning interactions among the profibrotic proteins transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF, CCN2), and ED-A fibronectin (ED-A FN) and the antifibrotic proteins tumor necrosis factor-α (TNF-α) and γ-interferon (IFN-γ).—Leask, A., Abraham, D. J. TGF-β signaling and the fibrotic response.

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fj.03-1273rev

TGF-beta signaling and the fibrotic response.

Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

结节病易误诊,据王洪武等~([1])收集国内18篇关于此病误诊的文献,误诊率高达63.2%,当然有误诊就会有误治,如孙永昌等~([2])报道26例结节病在影像学检查诊断的第一印象中拟诊结核5例,其中就有2例完成规范的抗结核治疗,为此应引起临床对本病诊治的重视。

Sarcoidosis

Steroidogenesis entails processes by which cholesterol is converted to biologically active steroid hormones. Whereas most endocrine texts discuss adrenal, ovarian, testicular, placental, and other steroidogenic processes in a gland-specific fashion, steroidogenesis is better understood as a single process that is repeated in each gland with cell-type-specific variations on a single theme. Thus, understanding steroidogenesis is rooted in an understanding of the biochemistry of the various steroidogenic enzymes and cofactors and the genes that encode them. The first and rate-limiting step in steroidogenesis is the conversion of cholesterol to pregnenolone by a single enzyme, P450scc (CYP11A1), but this enzymatically complex step is subject to multiple regulatory mechanisms, yielding finely tuned quantitative regulation. Qualitative regulation determining the type of steroid to be produced is mediated by many enzymes and cofactors. Steroidogenic enzymes fall into two groups: cytochrome P450 enzymes and hydroxysteroid dehydrogenases. A cytochrome P450 may be either type 1 (in mitochondria) or type 2 (in endoplasmic reticulum), and a hydroxysteroid dehydrogenase may belong to either the aldo-keto reductase or short-chain dehydrogenase/reductase families. The activities of these enzymes are modulated by posttranslational modifications and by cofactors, especially electron-donating redox partners. The elucidation of the precise roles of these various enzymes and cofactors has been greatly facilitated by identifying the genetic bases of rare disorders of steroidogenesis. Some enzymes not principally involved in steroidogenesis may also catalyze extraglandular steroidogenesis, modulating the phenotype expected to result from some mutations. Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis.

The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.

Objective
To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease.
Background
Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease.
Methods/Results
The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity).
Conclusion
The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.

MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)

Skin tumors occurring on the scleroderma fingers are rarely seen. Swollen fingers are hallmarks of systemic sclerosis, and mucin deposition in the lesional skin is a constant feature in systemic sclerosis. Here we describe a case of cutaneous myxoid cyst on the flexor aspect of the sclerotic fingers in a patient with severe diffuse cutaneous systemic sclerosis. Cutaneous myxoid cyst is a relatively common benign tumor; however, cases of cutaneous myxoid cysts developing on the scleroderma fingers have not been reported to date. Mucin deposition in the sclerotic skin may be a predisposing factor in the induction of myxoid cyst on the scleroderma finger in our patient.

/pdf/cutaneous-myxoid-cyst-on-the-sclerotic-finger-in-a-patient-6la7r4n3tp.pdf

Cutaneous myxoid cyst on the sclerotic finger in a patient with diffuse systemic sclerosis

Bullous Sweet's syndrome with myositis.

A 59-year-old male visited our department, complaining of red itchy papules on his right lower leg. Initially, the papules appeared on the dorsum of his right foot, and spread upwards to the shin. He had no infectious symptoms, such as throat pain and fever, prior to the development of the dermatosis. Physical examination revealed that a number of reddish papules and erythematous lesions with slight scales were distributed along Blaschko’s lines (Fig. 1a and b). Moreover, there were scaly erythema and vesicles between the third and fourth toes (Fig. 1c), and a potassium hydroxide preparation test detected a number of fungi (Fig. 1d). Unfortunately, a mycological culture was not carried out. He had not been aware of his tinea pedis. A biopsy specimen taken from the dorsum of the foot showed parakeratosis, individual cell keratinization, spongiosis, and liquefaction degeneration in the epidermis. Furthermore, red blood cell extravasation, hemosiderin deposition, and perivascular inflammatory cell infiltrates, mainly composed of lymphocytes, were observed in the upper dermis (Fig. 1e). Immunohistochemistry revealed a number of CD4as well as CD8-positive T-cells in the dermis, with a slight predominance of CD8positive epidermal T-cells (Fig. 1f). Other dermatitis showing linear distribution, such as inflammatory linear verrucous epidermal nevus, linear lichen striatus, and linear lichen planus were all ruled out. The patient was successfully treated with topical corticosteroid (betamethasone butyrate propionate) ointment.

/pdf/segmental-lichen-aureus-subsequent-to-interdigital-tinea-1gdk9cd8i9.pdf

Segmental lichen aureus subsequent to interdigital tinea pedis: A rare clinical appearance of “id”-reaction?

Dear Editor, A 43-year-old man with a 4-year history of severe nail dystrophy in all fingernails and toenails was referred to our department. Psoriatic skin lesions on his scalp and back had appeared 2 years previously. He did not complain of joint pain. He had previously been treated with oral cyclosporin (100 mg/day for a few months) and topical steroids, which were effective for the skin lesions, but not the nail lesions. The remaining nail dystrophy caused discomfort to the patient; however, the Dermatology Life Quality Index and Psoriasis Disability Index scores were just 1, respectively. On examination, pitting, marked subungual hyperkeratosis, onycholysis and periungual erythema were seen in all 20 nails (Fig. 1a). The Nail Psoriasis Severity Index (NAPSI) score calculated for all fingernails and toenails was 64. s.c. administration of adalimumab was started at a loading dose of 80 mg followed by 40 mg every 2 weeks. Five months later, there was no improvement in the nail lesions (Fig. 1b). We decided to switch adalimumab to infliximab at a dose of 5 mg/kg, i.v. administrated at week 0, 2, 6 and then every 2 month. A few months later, new healthy nails began to grow underneath the damaged nails, and then, 9 months after initiation of infliximab, all dystrophic nail lesions had greatly improved (NAPSI score, 8) (Fig. 1c). Our patient initially received adalimumab therapy; however, no improvement was observed in the nails even after 5 months of administration (10 doses in total). Because nail growth was not observed at all, we then switched to infliximab without dose escalation of adalimumab to 80 mg. Infliximab resulted in dramatic effects. Previous studies showed that NAPSI was improved in 95.1% of patients treated with infliximab, while 89.5% of those treated with adalimumab. Most of the biologics result in favorable effects on psoriasis involving the nail bed and matrix. Nail elongation speed is reported to be accelerated during treatment with biologics, along with sufficient efficacy. The lack of effect of adalimumab on nail growth in our case might have been because of severe subungual hyperkeratosis due to nail bed inflammation. Circulation abnormality was not observed. Although there are many reports that anti-tumor

Case of recalcitrant nail psoriasis unresponsive to adalimumab but successfully treated with infliximab.

https://doi.org/10.1016/j.abd.2022.04.015

Toshiyuki Yamamoto

Papers

Cutaneous myxoid cyst on the sclerotic finger in a patient with diffuse systemic sclerosis

Bullous Sweet's syndrome with myositis.

Segmental lichen aureus subsequent to interdigital tinea pedis: A rare clinical appearance of “id”-reaction?

Case of recalcitrant nail psoriasis unresponsive to adalimumab but successfully treated with infliximab.

Recurrence of psoriasis on the resolution sites left with lentiginous pigmented patches after TNF inhibitor therapy.