Disseminated cutaneous bacille Calmette-Guérin infection identified by polymerase chain reaction in a patient with X-linked severe combined immunodeficiency

An 8-month-old boy developed a disseminated cutaneous mycobacterial infection at 6 months of age that responded poorly to treatment. Further immunologic study and sequence analysis showed the presence of a missense mutation in the IL2RG gene, and X-linked severe combined immunodeficiency was diagnosed. To identify the strain of the microorganism causing the cutaneous infection, polymerase chain reaction with four pairs of primers was performed on skin biopsy specimens positive for acid-fast bacilli. Sequence analysis showed 99.36% homology with a bacilli Calmette-Guérin positive control. Disseminated bacilli Calmette-Guérin disease must be considered in any infant with cutaneous mycobacterial lesions, especially those with atypical histologic findings or who are immunocompromised. Testing by polymerase chain reaction using the proper primers may help in making a precise diagnosis.     

Epstein-Barr virus-associated primary central nervous system lymphoma in a patient with adult T-cell leukemia / lymphoma

We present a case of Epstein-Barr virus (EBV)-associated primary central nervous system lymphoma (PCNSL) arising from a patient with cutaneous-type adult T-cell leukemia/lymphoma (ATLL). Extranodal sites affected by ATLL include the skin, lung, liver, gastrointestinal tract and central nervous system (CNS). CNS involvement usually occurs as an acute and lymphoma-type ATLL. PCNSL is a rare type of tumor and the vast majority of PCNSL are of B-cell lineage. Individuals with acquired, iatrogenic or congenital immunodeficiency are at increased risk of PCNSL, which is commonly associated with EBV. In our patient, the expression of latent infection membrane protein 1 (LMP1), EBV nuclear antigen 2 (EBNA2), and EBV-encoded small RNA (EBER) in tumor cells confirmed a type III latency of EBV infection. Human T-cell lymphotropic virus type I (HTLV-I) can induce immunodeficiency before the overt development of ATLL. The HTLV-I infection led to suppression of the immune system and the development of EBV-associated PCNSL. This is the first reported case of the clinicopathological features of EBV-associated PCNSL arising from a patient with ATLL.     

Livedoid vasculopathy and hypercoagulability in a patient with primary Sjögren's syndrome

Background A 31‐year‐old woman presented with a 5‐year history of painful ulcerations, palpable purpura, porcelain‐white atrophic scars of the malleolar region and dorsal aspect of the feet, livedo reticularis on the limbs, arthralgia, xerophthalmia, and xerostomia. Methods Skin biopsy revealed vessel wall hyalinization and thrombosis of the microvasculature with a very scarce dermal inflammatory infiltrate. Biopsy of the oral mucosa showed mononuclear infiltration of an intralobular duct of a salivary gland. Results Laboratory studies, including autoantibodies and inflammation markers, were normal, except for a positive rheumatoid factor. Coagulation screening revealed C677T methylenetetrahydrofolate reductase (MTHFR) mutation, with a normal serum homocysteine. The patient was treated with oral methylprednisolone (32 mg/day with progressive reduction) and enoxaparin (20 mg/day subcutaneously), with complete ulcer healing within 4 months. Conclusion Livedoid vasculitis or vasculopathy has not been referred to previously in association with Sjögren's syndrome, but may be associated with other autoimmune disorders and anomalies of coagulation, namely factor V Leiden mutation, protein C deficiency, and MTHFR mutation, associated or not with hyperhomocysteinemia, a condition that seems to confer an increased risk of recurrent arterial and venous thrombosis. We stress the importance of anticoagulant therapy for ulcer healing and for the prevention of other thrombotic events.     

Prurigo pigmentosa in a patient with primary biliary cirrhosis and Sjögren syndrome

A 44‐year‐old Japanese woman suddenly developed severely pruritic erythematous papules on her trunk in a symmetrical distribution. Biopsy specimens showed the typical histopathological findings of prurigo pigmentosa. She had had recurrent episodes of high fever spikes for several years, and lost 10 kg in the last year. She was diagnosed as primary biliary cirrhosis (PBC) associated with subclinical Sjögren syndrome (SjS). Predonisolone (60 mg/day) for two weeks was effective for the PBC and fever, but not for the prurigo pigmentosa. PBC may be involved in the pathogenesis of this rare skin disease.     

Cutaneous ulcer in an immunosuppressed patient with adult onset Still's disease: primary cutaneous histoplasmosis?

Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum.Primary infection occurs through inhalation of spores from the air. Immunocompetent individuals are usually asymptomatic, but may develop pulmonary disease. Immunocompromised patients tend to present systemic histoplasmosis with cutaneous lesions occurring by secondary invasion. In this case report, we describe a probable primary cutaneous histoplasmosis (PCH) in a patient with adult onset Still''s disease under immunosuppression.     

Primary localized cutaneous amyloidosis with unusual clinical features in a patient with Sjögren's syndrome

A 69‐year‐old woman presented with a 2‐year history of an eczematous lesion covering the genital area. Histopathological examination showed deposits of amorphous, eosinophilic material and an infiltrate of plasma cells through the entire dermis into the subcutaneous fatty tissue. Congo red‐stained deposits showed apple‐green birefringence with polarizing microscopy. On immunohistochemistry, the deposited material was positively stained with anti‐κ light chain antibodies but not with anti‐λ light chain. A diagnosis of primary localized cutaneous amyloidosis (PLCA) was made, and the patient was also diagnosed as having Sjögren's syndrome (SjS) based on clinical and laboratory findings. The lesion of PLCA has spontaneously regressed over a period of 18 months. We report a unique case of PLCA and SjS that clinically demonstrated genital eczematous features and spontaneous involution, and we also describe a possible association between PLCA and SjS.     

Eruptive multiple lentigo-maligna-like lesions in a patient undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing colorectal carcinoma: a lesson for the pathogenesis of malignant melanoma?

Induction of multiple eruptive dermal and atypical melanocytic naevi has frequently been reported in children with malignant haematological diseases and chemotherapy-induced immunosuppression. This is the first report of an adult patient to develop multiple eruptive melanocytic skin lesions while undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing cancer. Our observation adds further evidence to the link between systemic (iatrogenic or intrinsic) immunosuppression and the induction of melanocyte proliferation and transformation.     

Relapsing Henoch-Schönlein purpura in an adult patient associated with hepatitis B virus infection

Henoch‐Schölein purpura is usually a disease of children presenting with arthralgia, abdominal pain, renal involvement, and palpable purpura. Viral and bacterial infections may have a role in its etiology. We present a 32‐year‐old male patient with recurrent Henoch‐Schölein purpura in association with a chronic hepatitis B infection of ten years duration. The patient had received lamuvudine and interferon‐α for the treatment of hepatitis B infection for a year. The skin lesions disappeared with the treatment of the hepatitis B infection. Four months after discontinuation of the therapy, the purpuric papules reappeared with reactivation of the hepatitis B infection. Although rarely reported, hepatitis B virus infection should be considered in patients with Henoch‐Schölein purpura.     

Salivary gland MALT lymphoma associated with Helicobacter pylori infection in a patient with Sjögren's Syndrome

We report a case of salivary gland MALT lymphoma in Sjögren's syndrome associated with localized H. pylori infection. A 76–year‐old woman had a history of bilateral cheek masses for two years. Histologically, the parotid glands were invaded by numerous centrocyte‐like cells to form lymphoepithelial lesions. The tumor cells showed immunohistological differentiation into B cells. Southern blotting demonstrated immunoglobulin gene rearrangement. These results indicated that the tumors were MALT lymphoma. H. pylori, as assessed by the urease test (CLO test; BML Ltd., Tokyo, Japan), was positive in the tumor specimen. After wide local excision of the tumors followed by radio therapy and oral administration of antibiotics and proton pump inhibitor, no evidence of recurrence was found during the 24–months of follow up. H. pylori infection in the salivary gland is rare, although the source of infection and transmission of H. pylori organisms has been thought to be the oral cavity. We discussed the association between H. pylori infection and salivary gland MALT lymphoma. The microorganism may play a role as an additional antigenic stimulus for the development of salivary gland MALT lymphoma as well as for the development of gastric MALT lymphoma. This means that H. pylori can play a role in lymphoma progression as booster of B cell lymphoproliferation.     

Painful indurated erythema suggestive of Kikuchi-Fujimoto disease in a patient with primary Sjögren's syndrome

We report a patient with primary Sjögren's syndrome who developed pyrexia, cervical lymphadenopathy, and painful indurated erythema on the forehead, back, chest, abdomen, and limbs. Laboratory data showed an elevated erythrocyte sedimentation rate, C‐reactive protein and CH50 in addition to existing autoantibodies including anti‐nuclear antibody, anti SS‐A antibody, and anti SS‐B antibody. A skin biopsy specimen showed focal infiltration of histiocytes with non‐neutrophilic karyorrhetic debris in the dermis and subcutaneous fat tissue. Immunohistochemically the infiltrated cells were stained for CD68, suggesting cutaneous involvement of Kikuchi‐Fujimoto disease. All symptoms and laboratory data improved within three weeks after treatment with 20 mg/day of prednisolone. The present case suggests that a pathophysiological condition similar to Kikuchi‐Fujimoto disease can develop during the long‐term course of Sjögren's syndrome.     

Birt-Hogg-Dubé syndrome in a patient with localized fibrofolliculomas and a novel mutation in the FLCN gene

Background Birt–Hogg–Dubé syndrome (BHDS) is characterized by skin fibrofolliculomas (FF), multiple lung cysts, spontaneous pneumothorax, and renal cancer. Cutaneous lesions are usually distributed over the face, neck, and upper trunk. The presence of FF confined to a circumscribed region of the skin has rarely been reported. Case report A 64‐year‐old woman presented with a 20‐year history of asymptomatic skin lesions located on the neck. Multiple skin‐colored papules with a clinical plaque‐like appearance were confined to the right side of the neck. Histopathological findings were typical for FF, and BHDS was suspected. The novel heterozygous mutation p.Val126SerfsX4 was identified in exon 5 of the FLCN gene. Colonoscopy, abdominal ultrasound, and abdominal thoracic scan revealed no associated pathologies, except for benign renal and hepatic cysts. Discussion To date, only two cases of localized FF in BHDS have been reported. Mutation analysis was not performed, but the authors considered the lesions to represent a localized variant of BHDS and speculated that this unusual form of the disease may be associated with a lack of visceral involvement as no signs of systemic disease were detected. Conclusions We identified the novel germline mutation p.Vall26SerfsX4 as responsible for this aspect of the patient’s phenotype, which suggests that alterations in the FLCN gene are also responsible for localized forms of BHDS. Moreover, the localized distribution of skin lesions may be related to a less severe form of the disease.     

Comparison of pegylated interferon α-2b plus psoralen PUVA versus standard interferon α-2a plus PUVA in patients with cutaneous T-cell lymphoma

Objective The aim of this study was to evaluate the safety and efficacy profile of pegylated interferon α‐2b (PEG‐IFN α‐2b) in combination with photochemotherapy (PUVA) in the treatment of cutaneous T‐cell lymphoma (CTCL) in comparison with standard IFN α plus PUVA. Design Retrospective cohort study over a period of 7 years. Patients and interventions A total of 17 consecutive CTCL patients (stage IA–IV) were retrospectively analysed for toxicity and response rates associated with PEG‐IFN α‐2b (1.5 μg/kg weekly) plus PUVA (n = 9) or standard IFN α‐2a (9 MIU 3×/week) plus PUVA (n = 8). Main outcome measures Differences of response rates (complete/partial remission), progression‐free survival, discontinuation of therapy, safety and toxicity profiles according to World Health Organization – Common Terminology Criteria of Adverse Events (WHO‐CTCAE). Results Myelosuppression and liver toxicity occured more frequently during PEG‐IFN α‐2b plus PUVA treatment than during standard IFN α‐2a plus PUVA therapy [77.8 vs. 50% (odds ratio 1.477) and 77.8 vs. 50% (odds ratio 1.692), respectively]. By contrast, the occurence of constitutional side‐effects (mainly fatigue) [100 vs.77.8% (odds ratio 0.889)] and more adverse events leading to study discontinuation was considerably higher in the standard IFN α‐2a plus PUVA group. The overall response rate in the PEG‐IFN α‐2b plus PUVA group (89%) was significantly superior. Conclusions In patients with cutaneous T‐cell lymphoma PEG‐IFN α‐2b plus PUVA might become a promising treatment alternative as its higher rate of myelosuppression and liver toxicity is outweighed by its lower percentage of constitutional side‐effects, and its significantly higher overall response. Due to the small number of participants at this retrospective study, a larger prospective study is essential to verify our results.     

Punctate keratoderma‐like lesions on the palms and soles in a patient with chloracne: a new clinical manifestation of dioxin intoxication?

We report what we believe to be a novel skin manifestation of dioxin intoxication. A 30-year-old woman with 2,3,7, 8-tetrachlorodibenzo-p-dioxin levels of 144,000 pg g-1 blood fat presented with severe chloracne that affected the entire integument. She also exhibited acral granuloma annulare-like lesions and distal onycholysis and, at a later time point, showed signs of hypertrichosis, as well as brownish-grey hyperpigmentation of the face. In addition, she developed punctate keratoderma-like lesions on the palms and soles. These lesions were negative for human papillomavirus and histologically characterized by cone-shaped hyperkeratoses invaginating, but not penetrating, into the dermis. Squamous syringometaplasia of the eccrine glands was observed in the immediate vicinity of these lesions. Both clinically and histologically these alterations are essentially indistinguishable from what is described as keratosis punctata palmaris et plantaris (KPPP). Although a fortuitous coincidence of chloracne and KPPP cannot be formally excluded, the possibility exists that in our patient toxic levels of dioxin were causally involved in this disorder of keratinization.