Infantile systemic hyalinosis: a clinicopathological study

Infantile systemic hyalinosis (ISH) is a presumed autosomal recessive connective tissue condition. Symptoms usually begin at birth or shortly thereafter, and are characterized by pain when handled, painful and swollen joints and, later on, dermal anomalies, diarrhea, failure to thrive and recurrent infections, which usually lead to death around the age of 2. The skin has generally diminished elasticity with small pearly papules appearing on neck, ears, coccygeal region, and face. We present two unrelated patients with ISH, with specific focus on clinical and pathologic studies. In the first patient the diagnosis was made several years after she died, in a retrospective study of her clinical file. On ultrastructural examination both patients showed an accumulation of fibrillogranular material in the extracellular matrix with long-spacing collagen of 90 nm. The first child died at the age of 1(1/2) years and the second at 3 years.     

A case of common variable immunodeficiency with intractable diarrhea and the functional disorder of renal tubules]

We report a case of a 31-year-old woman with common variable immunodeficiency (CVID) complicated with intractable diarrhea and the functional disorder of renal tubules. The patient became hypogammaglobulinemic after she suffered from measles at 6 years of age. She also suffered from lupus-like syndrome at 7 years of age. The complete remission was obtained by glucocorticosteroid treatment. An intravenous immunoglobulin replacement therapy was introduced at 11 years of age, since then her general condition was stable for more than 20 years. When she was 29 years old, she suffered from generalized malaise, anorexia with body weight loss, and numbness of face. The intractable diarrhea as protein loosing syndrome, and the severe abnormality of electrolyte balance with metabolic acidosis as the functional disorder of renal tubules were found. Her condition was not improved by the electrolytes or alkali replacement therapy. She was admitted for further evaluation and treatment. The intractable diarrhea and the functional disorder of renal tubules were dramatically improved after absolute restriction of food intake under hyperalimentation. When she began to take food, the symptom and sign became worse again. The interstitial nephritis and nonspecific inflammation of intestine were found by the tissue biopsy. The most characteristic finding was the infiltration of lymphocytes (predominantly CD 8 + T lymphocytes) in both intestinal mucosa and renal interstitium. The introduction of glucocorticosteroids improved her general condition and biochemical findings. This CVID case is complicated with intractable diarrhea and the functional disorder of renal tubules which is associated with the infiltration of CD 8 + lymphocytes in intestine and kidney. We consider that such case is very rare and valuable to report.     

Severe Liver Disorder Following Liver Transplantation in STING-Associated Vasculopathy with Onset in Infancy

Purpose

STING-associated vasculopathy with onset in infancy (SAVI) is a type-I interferonopathy, characterized by systemic inflammation, peripheral vascular inflammation, and pulmonary manifestations. There are three reports of SAVI patients developing liver disease, but no report of a SAVI patient requiring liver transplantation. Therefore, the relevance of liver inflammation is unclear in SAVI. We report a SAVI patient who developed severe liver disorder following liver transplantation.

Methods

SAVI was diagnosed in a 4-year-old girl based on genetic analysis by whole-exome sequencing. We demonstrated clinical features, laboratory findings, and pathological examination of her original and transplanted livers.

Results

At 2 months of age, she developed bronchitis showing resistance to bronchodilators and antibiotics. At 10 months of age, she developed liver dysfunction with atypical cholangitis, which required liver transplantation at 1 year of age. At 2 years of age, multiple biliary cysts developed in the transplanted liver. At 3.9 years of age, SAVI was diagnosed by whole-exome sequencing. Inflammatory cells from the liver invaded the stomach wall directly, leading to fatal gastrointestinal bleeding unexpectedly at 4.6 years of age. In pathological findings, there were no typical findings of liver abscess, vasculitis, or graft rejection, but biliary cysts and infiltration of inflammatory cells, including plasmacytes around the bile duct area, in the transplanted liver were noted, which were findings similar to those of her original liver.

Conclusion

Although further studies to clarify the mechanisms of the various liver disorders described in SAVI patients are needed, inflammatory liver manifestations may be amplified in the context of SAVI.

     

A case of eosinophilic cellulitis (Wells' syndrome)]

A 67-year-old man sustained a minor injury on the right hand after touching a potted plant. Several days later, he noted erythema and marked swelling on the right hand and forearm. The same lesions developed on the left hand and forearm. He also had pruritic erythema on the neck, trunk, and thighs. The initial clinical diagnosis was bacterial cellulitis and contact dermatitis. However, oral antibiotic and topical steroid therapy were not effective. Laboratory investigations revealed peripheral blood eosinophilia, elevated serum IgE level, and positive antinuclear antibody. Histopathological examination of a skin biopsy specimen showed an excessive infiltration of eosinophils and flame figures in the dermis. We diagnosed this case as eosinophilic cellulitis (Wells' syndrome). The skin lesions responded rapidly to the systemic oral steroid therapy. There has been no recurrence of eruption in 1 year of follow-up. The condition of the disease was correlated to peripheral blood eosinophil counts, and serum eosinophil cationic protein levels. However, serum interleukin-5 levels were within normal limits.     

Appearance of central nervous system lupus during corticosteroid therapy and warfarinization in a patient with pure red cell aplasia and antiphospholipid syndrome]

A 48-year-old woman presented to our hospital with epigastralgia and erythema on the left dorsalis pedis. Her medical history included deep venous thrombosis three months prior to admission to our hospital. Upon admission it was determined that she had severe anemia (hemoglobin level 4.6 g/dl). Bone marrow analysis indicated a markedly decreased number of erythroid progenitor cells. A skin biopsy specimen of the erythema revealed microthrombus. Anticardiolipin-beta2GPI antibody and lupus anticoagulant were positive. The patient was diagnosed with pure red cell aplasia (PRCA) and antiphospholipid syndrome (APS). After steroid pulse therapy and warfarinization, her anemia and purpura improved. Three months later she developed depression with positive anti-ribosomal P protein antibody that was indicative of central nervous system lupus. Although her psychometric condition did not respond to steroid pulse therapy, improvement was seen after she received three courses of cyclophosphamide pulse therapy. We report a rare case of CNS lupus that developed during corticosteroid therapy and warfarinization in a patient with PRCA and APS.     

Vulvar complications of urogenital schistosomiasis: study of 8 cases in Ségou, Mali

We present a retrospective study of eight cases of vulvar bilharziasis who attended our institution for dermatological visit from 1998 to 2001. The mean age was 11 years old (range: 7 to 13). The clinical examination found wart like or ulcerated nodules, papules and/or diffuse infiltration. All the lesions were located on the left side of the vulvae (labium) and/or the groin. S. haematobium was the only causative agent identified in all specimens. The exclusive left side location of the lesions reported here has never been mentioned in the previous studies. The physiopathology of this finding is possibly linked to factors similar to those explaining the Cockett syndrome. Further examinations, including ultrasonography of the pelvis in larger series, are needed to learn more about the mechanism of this clinical entity.     

A unique patient with an Ullrich-Turner syndrome variant and mosaicism for a tiny r(X) and a partial proximal duplication 1q

We report on an apparently previously undescribed neonatal diffuse congenital hyperkeratosis with spontaneous improvement. The child, born to consanguinous parents, presented at birth with a verrucous hyperkeratosis involving face, trunk, and limbs, but sparing palms and soles. No visceral or skeletal abnormality was associated and neurosensory status was normal. The skin condition improved dramatically during the first month of life. At age 7 years, the child was healthy with normal psychomotor development and growth. He had an abnormal curvature of nose, ulerythema ophryogenes, and large ears. The skin was moderately dry. This favorable clinical outcome led us to propose the term "regressive congenital hyperkeratosis" until further molecular characterization of this new phenotype.     

Relapsing annular erythema and myeloma successfully treated with cyclophosphamide

We report the history of a patient, who had recurrent patches of erythema on the trunk and extremities for some years. The diagnosis of erythema elevatum diutinum or annulare centrifugum was discussed. The patient developed a monoclonal IgA lambda fraction and clinical signs of myeloma. Treatment with cyclophosphamide stopped the development of erythema and also caused the M-component to disappear. This improvement has persisted even without cytostatic treatment. Another patient with prostatic carcinoma and relapsing annular erythema was cured of his skin lesions, when his carcinoma was treated with estrogens. The literature is reviewed.     

Primary effusion lymphoma with skin involvement

Primary effusion lymphoma (PEL) was once defined as a body cavity-based lymphoma without identifiable contiguous tumour mass, but is now recognised as an independent clinicopathological entity. The case of a 67-year-old Japanese woman with PEL is reported, in which the clinical findings showed a pericardial effusion and multiple erythema on the hypogastrium and inguinal region. The histopathological findings showed a diffuse infiltration of large neoplastic B cells from the dermis to the subcutis. After the disappearance of pericardial effusion without any treatment, she received several rounds of chemotherapy to resolve the skin eruption, but she finally died from multiple organ failure. No tumour mass was observed during the course of her disease.     

Case of subcutaneous and mesenteric acute panniculitis with Sj?gren's syndrome]

We report a case of a 27-year-old Japanese female with Sjogren's syndrome (SS), who suffered from several episodes of subcutaneous and mesenteric panniculitis with a recurrence within one year. After a history of fever and skin rash, the patient underwent surgery at a local hospital with a diagnosis of acute appendicitis complicated with an ileocecal abscess. She was also diagnosed as having SS. After the operation, the fever and skin rash persisted. She was treated with prednisolone (PSL), and her symptoms resolved. A recurrent bout of abdominal pain with fever, annular erythema on the trunk and a nodular erythematous rash on the lower extremities occurred six months after the operation. A skin biopsy from the lower extremities showed findings that were compatible with panniculitis. Abdominal computer tomography (CT) showed a diffuse swelling with soft tissue density in the intestinal mesenterium and para aortic area. A retrospective examination of the operative specimen obtained from the local hospital revealed centrilobular infiltration of neutrophils in the mesenteric adipose tissue with fat necrosis, which is compatible with mesenteric panniculitis. Twenty mg/day of PSL was successful in treating the systemic panniculitis, and the abnormal diffuse soft tissue density on the abdominal CT disappeared after three weeks of PSL administration. Systemic panniculitis is a rare complication in SS, and the pathogenesis is unclear.     

H1-receptor antagonists: effects on leukocytes, myth or reality?

H₁-receptor antagonists of the first and second generation have been used for many years to relieve symptoms arising from the action of histamine on the H₁ receptor. However, allergic inflammation is more than histamine release and action. Leukocyte infiltration during late allergic manifestations was demonstrated as being a hallmark of allergic inflammation. Second-generation H₁-receptor antagonists were studied in models of mast cell degranulation in vitro and of leukocyte infiltration in vivo . Analysis of the literature showed that a drug which is no more metabolized than cetirizine and fexofenadine allows a better relevance of in vitro models. Up to now, cetirizine was the only product in vivo able to reduce eosinphil infiltration in skin, nose, eyes and lungs during experimental allergenic challenges and late allergic inflammatory manifestations. Today, relevance of these properties can be seen in the recently published clinical results showing that cetirizine prevents the development of asthma in specifically sensitized infants with atopic dermatitis.     

Cowden syndrome complicated by schizophrenia: A first clinical report

Patients with Cowden syndrome exhibit mucocutaneous lesions, hamartomatous polyposis of the gastrointestinal tract, and macrocephaly, often complicated by malignant tumors, such as breast, thyroid, and uterine cancers. Autism spectrum and epilepsy have been known as neuropsychiatric symptoms associated with Cowden syndrome; however, to the best of our knowledge, there is no report on cases complicated by schizophrenia. Here, we report a first case of Cowden syndrome complicated by schizophrenia. A 49-year-old Japanese woman started experiencing auditory hallucinations in her teens. She had left breast cancer at the age of 34 years, and right breast cancer at the age of 37 years, all of which were surgically treated. She was also being treated by oral medications for Hashimoto's disease. On consulting her previous doctor for abnormal uterine bleeding that lasted for a year, she was diagnosed with endometrial cancer. However, immediately before surgery, her auditory hallucinations and paranoid delusions became severe, and she was referred to our hospital for detailed examination and treatment. No abnormalities were found on head MRI, and she was diagnosed with schizophrenia on the basis of neuropsychiatric examination findings. After her psychiatric symptoms were controlled by 2 mg of risperidone, she underwent surgery for endometrial cancer. Although there was no apparent family history, physical findings including macrocephaly and papillomatous skin lesions together with her past medical history of multiple malignant tumors suggested Cowden syndrome. Postoperatively, genetic testing revealed a pathogenic variant c.655C > T; p. Gln219* (NM_000314.4) in PTEN, leading to the confirmation of the diagnosis of Cowden syndrome.     

A case of dermatomyositis associated with different types of cancers at intervals of six years]

The patient is a 56-year-old Japanese woman who suffered from breast cancer and ovarian cancer at intervals of 6 years, and was also complicated by two episodes of dermatomyositis, each of which occurred simultaneously with each of two cancers. When she was 51 years old, she developed dermatomyositis for the first time 6 months after the resection of breast cancer, whose histological type was tubular adenocarcinoma. The dermatomyositis remitted without oral corticosteroids in 2 months, and the remission had continued for 6 years. However, at the age of 56, dermatomyositis abruptly recurred with a pruritic generalized rash, Gottron's papules and elevated serum CK levels. Examination for malignancy revealed an ovarian tumor, which was diagnosed as serous papillaly adenocarcinoma, and the surgery was performed. After the resection of the ovarian cancer, skin rash was improved dramatically and CK levels were normalized again without oral corticosteroids. Since there were no evidences of recurrence of the breast cancer, it was considered that each episode of dermatomyositis was associated with each of the cancers, respectively. We report this rare and interesting case to consider the etiology of cancer-associated myositis as a paraneoplastic syndrome, since the two cancers have different histological types.     

Case of acute generalized exanthematous pustulosis caused by Kerorin]

A 78-year-old woman visited a local clinic because of cough and fever, and was prescribed levofloxacin, carbocisteine, and cold medicine (salicylamide, acetaminophen, anhydrous caffeine, promethazine methylene disalicylate). The following day, erythema appeared on the trunk, and spread. Multiple pustules independent of hair follicles developed on the erythema mainly in the skin folds. Histopathological examination revealed subcorneal pustular dermatosis. The clinical course and characteristics of the rashes led to a diagnosis of acute generalized exanthematous pustulosis (AGEP). Although the administration on levofloxacin, carbocisteine, and cold medicine were discontinued, the rashes recurred. We reviewed the patient's history, and found that she had a history of taking the over-the-counter drug Kerorin, and had taken a dose of Kerorin on the day before the first examination and before the recurrence. The ingestion of Kerorin was regarded as an incidental oral administration test, which was positive. Thus, oral administration tests with Kerorin and its ingredients acetylsalicylic acid and anhydrous caffeine were positive, leading to a diagnosis of AGEP caused by Kerorin.     

Biotin deficiency in amino acid formula nutrition for an infant with milk protein allergy]

We reported a 4-month-old girl with biotin deficiency caused by amino acid formula. Two weeks after birth, she was diagnosed as having a milk protein allergy. After switching to amino acid formula from usual formula, her symptoms and laboratory findings became normal. About three weeks after the beginning of amino acid formula, she developed intractable skin erosions around the eyes, mouth, neck, and anogenital area. By measuring concentrations of some trace elements, she was diagnosed as having a biotin deficit, because of the organic aciduria and undetectable serum biotin concentration. Her serum biotinidase level was normal. Upon administration of oral biotin supplementation, all her symptoms and laboratory findings were dramatically improved. Since amino acid formula contains very few biotin, we should pay attention to biotin deficiency when infants receiving amino acid formula.     

Successful bosentan therapy in a case of pulmonary arterial hypertention developed during immunosuppressive therapy for lupus nephritis

We report a 43-year-old female who developed pulmonary arterial hypertension (PAH) during intensive immunosuppressive therapy for systematic lupus erythematosus (SLE). She was diagnosed as SLE at the age of 32 years based on serological and hematological abnormalities, oral ulcers, and facial erythema. She experienced frequent flare-ups of disseminated discoid lupus between the ages of 33 and 36 years and developed immune thrombocytopenia at the age of 39 years. In 2007 when she was 43 years old, she developed lupus nephritis (LN) with elevated serum anti-double stranded DNA antibodies and urine protein of less than 1 g/day. Combination therapy for the LN with 35 mg/day prednisolone and intravenous cyclophosphamide (IVCY) led to renal remission. After the seventh monthly session of IVCY, she developed dyspnea on exertion. PAH was diagnosed based on enlarged main pulmonary arteries on the chest x-ray, right ventricular outflow and a peak tricuspid regurgitant pressure gradient exceeding 45 mmHg on echocardiography, an elevated plasma brain natriuretic peptide (BNP) level of 260 pg/ml, the exclusion of pulmonary thromboembolism, and no lung fibrosis. The PAH was treated successfully with bosentan. At present the tricuspid regurgitation has disappeared, and the plasma BNP level has normalized.     

Hereditary angioedema: a family study

Hereditary angioedema (HAE) is a rare, life-threatening, autosomal dominant disease characterized by recurrent episodes of angioedema, and caused by a deficiency of the plasma protein C1-esterase inhibitor (C1-INH). Clinical manifestation of HAE may first develop during childhood but typically presents around puberty with nonpruritic and non-pitting edema of the subcutaneous and mucosal tissues. Up to now, there has been no published report of HAE case in Taiwan. We reported a 33 year-old female patient who had recurrent painful swelling of face and hands since 27 years of age. She first suffered from sudden onset of painful swelling of the eyelids and lips in August 1998 when she was pregnant for the first time. Subsequently, similar episodes recurred for a few times. Her blood test disclosed that her C3 and C4 were 125 mg/dl and 6 mg/dl, respectively. Her uncle died of laryngeal edema at the age of 30 years. Her father and elder brother also had the similar history of recurrent facial and hand swelling. The C4 levels of her elder brother were 6 mg/dl and 13.3 mg/dl on two separate occasions. The C1-INH antigen serum level and functional assay of the index patient and ten other family members were studied. A total of seven members of the family were confirmed to have type 1 HAE as evidenced by the low C4 and low C1-INH antigenic level and functional activity. Two of the seven cases were asymptomatic up to the date of our report.     

Erythema multiforme and its clinicopathological disorders in a horse

A case of erythema multiforme in an 11-year-old mare which had received no medication is presented with a history of foaling. This horse displayed a gradual outbreak of erythematous macules, raised papules, and nonalopecic and nonpruritic plaques over the lateral aspects of the neck and shoulders to rump without involvement of the dorsum and ventral abdomen. The distribution of these skin lesions was bilateral but asymmetric. Histopathological findings included mild hydropic degeneration and scattered apoptotic keratinocytes especially at different layers of the epidermis. The dermis showed a marked full-thickness edema particularly at epidermodermal junction with moderate diffused infiltration of mixed eosinophils, lymphocytes, plasma cells, and macrophages at different portions of the dermis. Presence of the eosinophils was very notable. An inciting etiology could not be identified in this case. Affected horse had spontaneous remission without drug therapy within 3.5 months.     

Nocardia brasiliensis infection seen on grafted skin of the dorsum of a foot.

For the past 4 years a 23 y-old female has noticed erythema on the dorsum of the right foot, where skin was grafted due to a traffic accident 20 years ago. She visited the Department of Dermatology of Gifu Prefectural Hospital on Oct. 19, 1998; her general health was good. Physical examination disclosed a swelling with erythema, papules and pustules on the dorsum of the right foot. The results of routine laboratory investigations were within normal limits except for the white blood cell count (11,300/mm(3)), blood sediment rate (25 mm/hrs), C reactive protein (1.21) and rheumatoid factor (x 16.6). Several yellowish and verrucous or wrinkled colonies were grown on Sabourauds agar culture from the biopsied specimen of the foot. Histopathological features showed epidermal hyperplasia with elongation of rete ridges and granulomatous changes in the dermis; many mononuclear and giant cells were present, and several positive fine filamentous and irregularly branching structures with PAS and Grocott stains were seen in the granulomatous nests. Both clinical and histopathological features led to speculation of Nocardia infection, and Nocardia brasiliensis was determined. The patient was treated by surgical total resection including the grafted skin. Although a soybean-sized nodule was seen on the border of the skin-graft of the foot three months later, there was no recurrence after the local resection.