Jihong Li ,Yan Wang ,Xiao Dan ,Yi Chen ,Yuanxia Zou ,Chunhua Zhong ,Min Tong,Xiaoyu Wu,Jiayu Zhang*

1Department of Dermatology,Leshan Traditional Chinese Medicine Hospital,Leshan,Sichuan 614000,China.2Department of Medical Cosmetology,Dali University,Dali,Yunnan 671003,China.3Department of Dermatology,The People's Hospital of Ya An,Yaan,Sichuan 625099,China.4Department of Newborn Medicine,Hospital(T.C.M)Affiliated to Southwest Medical University,Luzhou,Sichuan 646000,China.

Abstract The patient is a 37-year-old male with a right anterior tibial mass for more than one year and a left anterior tibial mass for more than one month.There was a history of hyperthyroidism.Histopathology of the lesions showed epidermal hyperkeratosis of the skin tissue,thickening of the spinous layer,extensive collagen fibrillation in the superficial dermis and reticular layer,and numerous linear and granular mucoprotein deposits in the lower and middle dermis.Blastocystis hominis was routinely detected in the stool.Diagnosis:1.Pretibial myxedema 2.intestinal parasitosis(Blastocystis hominis infection).

Keywords:pretibial myxedema;hyperthyroidism;blastocystis hominis infection

Clinical Data

The patient is a 37-year-old male with a right anterior tibial mass for more than 1 year and a left anterior tibial mass for more than 1 month.The patient found a bulging bean-shaped nodule on the right anterior tibial area with a smooth surface 1 year ago,and the lesion gradually increased to the size of an egg and extended to the left anterior tibial area 1 month ago.The patient went to a pharmacy to buy "Compound Dexamethasone Acetate Cream" for topical application without relief.In 2013,he was treated with I131in a local hospital for hyperthyroidism,which led to hypothyroidism and long-term use of Levothyroxine Sodium Tablets for thyroid hormone supplementation.He had no previous gastrointestinal diseases and no patients with similar diseases in his family.

Physical Examination:The general condition was good.Both eyes were slightly protruding.The thyroid gland boundary was unclear and not palpable.Superficial lymph nodes of the whole body were not palpable and enlarged.Dermatological examination:about 7 × 6 cm size mass was seen in the right calf anterior tibia,4 × 3 cm size mass was seen in the left calf anterior tibia,the skin of bilateral masses became thickened and hardened,the boundary was unclear,the texture was medium to touch,no indentation,no evident mobility.The skin was tense and shiny,dark red,and the right calf anterior tibial skin had an enlarged follicular opening at the early stage of the lesion,rough skin,and a mild orange peel-like appearance.

Laboratory Tests:thyroid-stimulating hormone (TSH):9.740 uIU/ml(0.55～4.78 uIU/ml),free triiodothyronine(FT3):3.63 pmol/L(3.5～6.5 pmol/L),free thyroxine (FT4):18.55 pmol/L (11.5～22.7 pmol/L).Liver function and blood routine did not show any significant abnormalities.Blastocystis hominis was routinely detected in the stool.

Vascular ultrasound examination:Right calf "mass"exploration:skin and subcutaneous tissue thickening,echogenic enhancement,range of about 74 × 17 × 62 mm,no envelope,unclear boundary.CDFI:no obvious blood flow signal was seen.Left calf "mass" exploration:the skin and subcutaneous tissue were thickened and echogenically enhanced,with an area of about 43 × 7.6 × 29 mm,no envelope,unclear boundary.CDFI:no significant blood flow signal was seen.The examination findings suggested that the lower legs' skin and subcutaneous tissues were thickened and echogenically enhanced bilaterally.

Histopathological examination:the skin tissue was hyperkeratotic in the epidermis,thickened in the spinous layer,and partially papillary hyperplasia.Extensive collagen fibers were increased in the superficial and reticular layers of the dermis,and large amounts of linear and granular mucin deposits were seen in the middle and lower dermis,with some collagen fiber breaks and small foci lymphocytic infiltration.

Diagnosis:1.Pretibial myxedema 2.intestinal parasitosis(Blastocystis hominis infection)

Treatment:Department of Endocrinology adjusted thyroid hormone therapy,adjusted levothyroxine dose to 75 ug PO Qd.Department of dermatology used metronidazole tablets 100 0.4 g PO Tid.After 2 months of follow-up,both lower leg's anterior tibial nodules became softer and tended to shrink.

Figure 2 Blastocystis hominis can be observed under the microscope.(A) Low magnification view of Blastocystis hominis.(B) High magnification view of Blastocystis hominis.

Figure 3 Ultrasound images of both lower leg vessels in a patient with pretibial myxedema.(A) Ultrasound image of the anterior tibial vessels in the right lower leg.(B)Ultrasound images of the anterior tibial vessels in both lower legs.

Figure 4 Skin histopathology images of pretibial myxedema (× 100).(A) The skin tissue was hyperkeratotic in the epidermis,thickened in the spinous layer,and partially papillary hyperplasia.(B)large amounts of linear and granular mucin deposits were seen in the middle and lower dermis.

Discussion

Pretibial myxedema is a skin lesion caused by the deposition of mucin that occurs in the anterior tibial skin.The etiology of pretibial myxedema is still unclear and is mostly associated with autoimmune reactions.It can be triggered by local trauma,infection,and pressure and is most often seen in toxic diffuse goiter,often accompanied by hypermetabolic syndrome,goiter,and ophthalmoplegia [1].Clinically,pretibial myxedema can be divided into three types:limited type,diffuse type,and elephantiasis type.TSH receptor-like immunoreactive proteins have been discovered in the skin of patients with pretibial myxedema,whose receptors and antibodies can activate fibroblasts in concert with cytokines secreted by lymphocytes.The receptors and antibodies can activate the fibroblasts with cytokines secreted by lymphocytes.The action of autoimmunity and cellular immunity induces fibroblasts to proliferate and secrete large amounts of aminoglucan and deposit it in the dermis and subcutis,thus causing local mucinous edema [2].

It is currently believed that the cause of pretibial myxedema occurring in the anterior tibia is related to mechanical factors.Trauma induces T-cell activation and triggers an antigen-antibody response,which stimulates fibroblast activation and increased deposition of mucin synthesis leading to edema,which causes local lymphatic reflux impairment and exacerbates the immune injury.Additionally,bruxism dermatitis due to local microcirculation disorders caused by varicose veins can cause pretibial myxedema in patients with normal thyroid function,while hypoxia can increase hyaluronic acid production and form excessive mucin deposits.Patients with chronic lymphocytic thyroiditis,primary hypothyroidism,and post-thyroid surgery are prone to pretibial myxedema.

Blastocystis hominis is a single-celled protozoan parasite that lives in the intestinal tract of humans and animals,mainly in the ileocecal region of the human intestine,and can cause abdominal pain,diarrhea,and other gastrointestinal symptoms after infection [3].Blastocystis hominis infection can lead to barrier effects at the parasite site and damage to the intestinal mucosal epithelium,resulting in impaired intestinal digestion and absorption,disruption of the intestinal microbiome,and the development of immune responses and inflammation.Different cytokines can be affected by Blastocystis hominis infection.IL-5 stimulates cell proliferation and differentiation,enhances eosinophil viability,and kills blastocystis hominis [4].IL-6 promotes cell activation and proliferation and eventually differentiates them into plasma cells,increases immunoglobulin synthesis,and stimulates cytotoxic cytokine responses [5].IL-8 enhances host defense responses and anthelmintic effects by participating in the local immune response in the intestinal mucosa following blastocystis hominis infection.IL-8 inhibits the adhesion of neutrophils to cytokine-activated endothelial cell monolayers and increases the killing capacity of inflammatory cells[6].

Granulocyte-macrophage colony stimulating factor (GM-CSF)modulates mucosal immune,and inflammatory responses mediate cytotoxic effects and phagocytosis by polymorphic neutrophils.GM-CSF initiates cellular immune responses in blastocystis hominis and promotes inflammatory responses in the intestinal mucosa [7].Epidermal growth factor (EGF) regulates the proliferation of intestinal epithelial cells.Blastocystis hominis infection decreases intestinal EGF and receptor levels,leading to intestinal barrier dysfunction,damage to intestinal epithelial cells,and increased permeability,causing pathophysiological changes in the intestine [8].

For the treatment of pretibial myxedema,currently available methods include topical glucocorticoid therapy,which is usually recommended for mild and severe cases and has efficacy for symptomatic relief [9].Physical compression and decompression therapy,indicated for use in the elephantiasis type to improve lymphedema.Immunotherapy and surgical treatment.Most pretibial myxedema cases do not require specific treatment and may heal on their own after several years.In addition,control of risk factors such as smoking,aggressive treatment of Graves' disease and infiltrative proptosis,and systemic immunomodulatory therapy may play a preventive and adjunctive role in treating pretibial myxedema [1].

This patient is characterized by pretibial myxedema occurring after years of hyperthyroidism and combined with blastocystis hominis infection,a rare type that is easily misdiagnosed.The lesion was slightly changed,and treatment with metronidazole and thyroid hormone modulation was effective.Therefore,when myxedema at any site is encountered clinically,the patient should be further examined.