Lymphocutaneous type of nocardiosis caused by Nocardia brasiliensis: a case report and review of primary cutaneous nocardiosis caused by N. brasiliensis reported in Japan

Nocardiosis is a mixed suppurative and granulomatous inflammatory disease caused by infection with Nocardia organisms, a group of aerobic actinomycetes. We recently encountered a 25-year-old woman with posttraumatic nocardiosis of the lower extremities. The clinical symptoms noted during her first visit included erythematous swelling of the right knee accompanied by white maceration of the center of the knee and erosions, shallow ulcers and satellite pustules. In addition, multiple erythematous areas (up to the size of the tip of the thumb) were linearly distributed on the right thigh. These lesions were painful, and right inguinal lymphadenopathy was also noted. No lesion was found in internal organs such as the lungs. Histopathologically, signs of nonspecific granulomatous inflammation were observed, as well as several filamentous branching bacilli positive on Grocott stain. The organisms isolated from culture of pus were acid-fast, Gram-positive long rods. The isolated strain was finally identified as Nocardia brasiliensis. The patient was therefore diagnosed with lymphocutaneous type of primary cutaneous nocardiosis caused by N. brasiliensis. Drip infusion of flomoxef sodium was initially performed to treat her condition. Because of exacerbation of erythematous swelling of the right knee and an increase in number of pustules, treatment was switched to oral minocycline hydrochloride therapy. The disease healed 9 weeks after the start of oral minocycline hydrochloride therapy. Our patient was free of systemic immunosuppression and was neither under 10 nor over 65 years of age. She may therefore be considered a rare case of lymphocutaneous type of nocardiosis. We present this case and discuss reported cases of primary cutaneous nocardiosis due to N. brasiliensis in Japan.     

Primary Lymphocutaneous Nocardiosis Due to Nocardia otitidiscaviarum: The First Case Report from Japan

We report a case of lymphocutaneous syndrome caused by Nocardia otitidiscaviarum (formerly known as N. caviae) in a 78-year-old woman who underwent long-term therapy with prednisolone for bronchial asthma. Histological examination showed granulomatous reaction with multiple polymorphonuclear leukocytes and revealed a Gram positive filament in the dermis. Grampositive, slightly acid-fast branched filaments were also found in the smear of the purulent material. The cell wall constituents of the isolate were meso-diaminopimelic acid, arabinose, and galactose; the mycolic acid pattern of the isolate was Nocardia type. The organism decomposed xanthine and hypoxanthine, but not tyrosine or casein, which distinguished it from N. asteroides and N. brasiliensis. The skin lesions responded to minocycline and later to a combination of doxycycline and ofloxacin. This primary lymphocutaneous nocardiosis due to N. otitidiscaviarum is the first in Japan.     

A Case of Lymphocutaneous Nocardiosis with a Review of Lymphocutaneous Nocardiosis Reported in Japan

An 82-year-old Japanese male developed nodules and ulcers along the lymphatics after a fall in the garden of his house resulting in injuries to the dorsum of his left hand which lasted for 3 months. Nocardia brasiliensis was isolated from a nodule, supporting a diagnosis of the lymphocutaneous type of nocardiosis. He had previously developed generalized bone metastasis from prostatic cancer, and his resulting depressed immunity might have played a part in the nocardiosis genesis. Sixteen cases of the lymphocutaneous type of nocardiosis reported in Japan were reviewed.     

Mycetoma caused by Nocardia caviae in the first Brazilian patient

Background  Mycetoma is a chronic subcutaneous mycosis caused by exogenous fungi or actinomycetes. This infection has a progressive course and shows a typical clinical characteristic of tumefaction, draining sinuses, and grains. Infection initiation is related to local trauma and can spread to muscle, underlying bone, and adjacent organs. Nocardia brasiliensis is the most frequent actinomycete isolated, while N. caviae is a rare agent. Methods  We present a case of mycetoma in a 37‐year‐old African‐American man on the right hand. The infection had been apparent for four years prior to the consultation. When the infection did not respond to antibiotic therapy, the patient was referred to the Dermatology department. Routine laboratory studies were normal. X‐ray examination of the hand showed an osteolytic lesion on the hand bones. On skin biopsy culture, on Sabouraud Dextrose Agar at 28 °C, a colony was isolated which was further identified as N. caviae by biochemical and hydrolysis testing. Results The patient was treated with oral trimethoprim/sulfamethoxazole (TMP/SMZ) 160/800 mg twice a day for 10 months. Four months after the beginning of the therapy, the subject exhibited clinical improvement and functional recovery of the hand. Five‐year follow‐up X‐ray examination of the hand showed no osteolytic lesion on the hand bones. Conclusion We report the first mycetoma case caused by N. caviae in our country with an unusual location on the hand. The patient showed clinical improvement with oral TMP/SMZ.     

Lymphocutaneous nocardiosis caused by Nocardia asteroides. Case report and literature review

A 22-year-old man developed erythematous nodules and an ulcer mimicking sporotrichosis on his right hand and forearm, which was subsequently diagnosed as lymphocutaneous nocardiosis caused by Nocardia asteroides. To our knowledge, 21 cases of lymphocutaneous nocardiosis have been reported, with the majority of those cases, except for a few that remain uncertain, being due to Nocardia brasiliensis. The case reported herein, the first known definitive case caused by N asteroides (to our knowledge), showed a more chronic course and less inflammatory manifestation compared with that caused by N brasiliensis. This is probably because N brasiliensis has a stronger virulence than N asteroides.     

Primary cutaneous nocardiosis caused by Nocardia brasiliensis following a wasp sting

We report a case of an 87‐year‐old woman who presented with painful erythema of her right forearm 10 days after she had been stung by a wasp on her right hand. The lesion had rapidly deteriorated during the week before presentation, and treatment with antibiotics and glucocorticoids did not improve the condition. After careful evaluation, we performed cultures from the lesion aspiration, and morphological and genetic analysis of bacteria cultures confirmed a bacterial infection with Nocardia brasiliensis. The patient recovered after 3 weeks. Primary cutaneous nocardiosis due to Nocardia spp. is relatively uncommon in clinics, but it was the distance of the lesions from the affected area of the wasp sting that has made this an even rarer case and of interest to report.     

PRIMARY CUTANEOUS NOCARDIA INFECTION DUE TO NOCARDIA ASTEROIDES

A 34-year-old white man was admitted to the hospital for treatment of cyclosporine toxicity. He was referred to the dermatology service for the evaluation of two lesions that had been present for 4 weeks on the dorsum of his left hand. The patient stated that he had cut his hand on a fence and later cleaned his aquarium two weeks before the skin lesions appeared. The past medical history was significant for a cadaveric renal transplant in 1984 for renal agenesis of the left kidney and obstructive nephropathy of the right kid-ney. His oral medications included methylprednisolone, dil-tiazem, ranitidine, cyclosporine, and ketoconazole. The recent addition of ketoconazole for oral thrush was felt to have caused the cyclosporine toxicity. The patient was cushingoid in appearance with promi-nent generalized hypertrichosis. The vital signs and the chest examination were normal. Skin examination revealed a 6-mm tense vesicle with surrounding erythema with an adjacent 5-mm firm linear papule (Fig. 1). There was no lymphadenopathy. Both lesions were biopsied, hemisec-tioned, and sent for routine light microscopy and for fungal, atypical mycobacterial, and bacterial cultures. Laboratory studies were significant for a blood urea ni-trogen of 56 mg/dL, creatinine of 2.6 mg/dL, WBC of 13,100/mm¹³, and a cyclosporine level of 2333 ng/mL (thera-peutic level 100–300 ng/mL). X-ray of the left hand showed no abnormality. Chest x-ray and computerized axial tomog-raphy scan revealed a widened superior mediastinum sec-ondary to mediastinal lipomatosis. Tissue cultures grew Nocardia asteroides. Bacterial and mycobacterial cultures, including atypical mycobacteria, were negative. The biopsy showed a mixed cellular infiltrate with scat-tered multinucleated giant cells and focal microabscesses. Brown and Brenn stain showed gram-positive filamentous organisms. A modified Fite stain (Fig. 2) demonstrated acid-fast filamentous organisms. The patient was diagnosed as having primary cutaneous nocardiosis with no evidence of dissemination. He was treated with trimethoprim sulfamethoxazole (TMP/SMX), one tablet orally four times daily, with resolution of the skin lesions within 3 weeks, but the patient developed neurolog-ic toxicity and elevation of his serum creatinine with this therapy. He was unable to tolerate a lower dose of TMP/SMX and the medication was changed to sulfisoxazole 500 mg orally four times daily, with plans to continue the treatment for 12 months. There has been no recurrence after almost 12 months of therapy.     

Cutaneous nocardiosis: report of two cases and review of the literature

Background Cutaneous nocardiosis is an uncommon infectious disease that presents as a primary cutaneous infection or as a disseminated disease. It is often misdiagnosed because of its rarity and nonspecific clinical picture. Methods We report a case of each type. The first case is an immunocompetent patient who was infected by Nocardia while gardening and developed a superficial skin infection – one of the three clinical manifestations of primary cutaneous nocardiosis. The second case is an immunocompromised patient with pulmonary nocardiosis that extended to the skin as part of a disseminated disease. Results The immunocompetent patient with primary cutaneous nocardiosis had the classical features of a superficial skin infection. He had a nodular–pustular lesion on the right arm, which appeared 7 days after gardening with bare hands. Nocardia was identified in a skin culture taken from a pustule, unfortunately not to the species level. Treatment with minocycline for 3 months resulted in full remission of the lesion. The immunocompromised patient with disseminated nocardiosis had high fever, productive cough, hemoptysis, and erythematous nodules and pustules on the extremities. N. brasiliensis was isolated from bronchial samples and skin. Treatment with a high dose of trimethoprim and sulfamethoxazole for five months resulted in full recovery from cutaneous and pulmonary complaints. No relapse of the infection was found on follow‐up in either patient. Conclusion These cases demonstrate the need for a high degree of suspicion, focused clinical search, and appropriate laboratory procedures in the diagnosis and management of cutaneous nocardiosis.     

Cutaneous nocardiosis caused by Nocardia brasiliensis after an insect bite.

We report the case of a primary lymphocutaneous nocardiosis occurring on the right calf of a healthy 56-year-old man after an insect bite. Analysis of the purulent exudate obtained from the nodule revealed Nocardia brasiliensis. The initial therapy with trimethoprim-sulfamethoxazole had to be stopped due to a drug eruption. However, with minocycline treatment the patient recovered within 5 weeks. Superficial (sporotrichoid) infections and a history of outdoor injury should be considered suspicious for cutaneous nocardiosis.     

Acute lymphangitic nocardiasis

The third case of lymphangitic nocardiasis caused by Nocardia brasiliensis to be recorded in Uruguay is presented. The clinical picture showed some of the features of sporotrichosis, but it was more acute, the nodules developing rapidly into abscesses. A review of eight similar cases, reported previously, reveals that N. brasiliensis was properly identified in five of them. All cases were localized on the upper limbs, and granules were not seen on direct examination. Mycetomas caused by N. brasiliensis have not been observed in Uruguay.     

A novel case of nocardiosis with skin lesion due to Nocardia araoensis

Nocardiosis is caused by gram-positive aerobic actinomycetes that live in soil and are known to be responsible for opportunistic infections. The condition mostly affects the lung, brain or skin. Here, we present a 24-year-old Japanese woman who had had systemic lupus erythematosus since the age of 20 years, and lupus nephritis since the age of 23 years. She developed cutaneous lymph duct-type nocardiosis due to Nocardia araoensis while on immunosuppressant therapy. The patient had cutaneous findings from the right inguinal region to the right lower thigh and did not have lesions on the rest of the body. Minocycline and co-trimoxazole were co-administrated, and her condition improved. To our knowledge, this is the first case in which N. araoensis was detected by analysis on rRNA base sequence in skin lesions.     

Pentamidine in Pneumocystis jirovecii prophylaxis in heart transplant recipients

Despite advances in transplantation techniques and the quality of post-transplantation care, opportunistic infections remain an important cause of complications. Pneumocystis jirovecii (P. jirovecii) is an opportunistic organism, represents an important cause of infections in heart transplantation patients. Almost 2% to 10% of patients undergoing cardiac transplantation have Pneumocystis pneumonia. Prophylaxis is essential after surgery. Various prophylaxis regimes had been defined in past and have different advantages. Trimethoprim/sulfamethoxazole (TMP/SMX) has a key role in prophylaxis against P. jirovecii. Generally, although TMP/SMX is well tolerated, serious side effects have also been reported during its use. Pentamidine is an alternative prophylaxis agent when TMP/SMX cannot be tolerated by the patient. Structurally, pentamidine is an aromatic diamidine compound with antiprotozoal activity. Since it is not effectively absorbed from the gastrointestinal tract, it is frequently administered via the intravenous route. Pentamidine can alternatively be administered through inhalation at a monthly dose in heart transplant recipients. Although, the efficiency and safety of this drug is well studied in other types of solid organ transplantations, there are only few data about pentamidine usage in heart transplantation. We sought to evaluate evidence-based assessment of the use of pentamidine against P. jirovecii after heart transplantation.     

皮肤淋巴管型孢子丝菌病1例

患者女,57岁。右拇指、腕部及前臂结节伴瘙痒和疼痛3月。右前臂皮损组织病理示:化脓性肉芽肿性改变。真菌培养见申克孢子丝菌生长。诊断:皮肤淋巴管型孢子丝菌病。     

Primary cutaneous nocardiosis in immunocompetent children

Primary cutaneous nocardiosis is an infrequent opportunistic infection that mainly affects immunodepressed hosts. We describe two immunocompetent patients who exhibited two clinical forms of cutaneous nocardiosis, a mycetoma from walking barefoot in contaminated water and in the case of the other patient a lymphocutaneous form on the basis of a stabbing-cutting injury. In both cases the tests performed ruled out any immunodeficiency, particularly chronic granulomatose disease, since nocardiosis is regarded as an infection that acts as a marker for that illness. Treatment with cotrimoxazole led to the total healing of the lesions in both patients.     

Predicting possible zonisamide hypersensitivity syndrome

Abstract: Zonisamide (ZNS) is an anticonvulsant (AC) that contains a sulpha moiety potentially triggering hypersensitivity syndrome reactions (HSR). The lymphocyte toxicity assay (LTA) is an in vitro drug rechallenge test, which is believed to reflect a decreased capacity of the individual to detoxify reactive metabolites. The study examined whether cross‐reactivity is present between ZNS and other AC and/or sulphonamides and if this HSR may be predicted using the LTA. The second aim was to determine age‐related differences in ZNS‐induced HSR. LTA was previously validated in patients who received sulphamethoxazole (SMX) or AC. Methods: Forty adult patients who displayed clinical HSR to SMX (20) or AC (20) participated in the study. Each group was represented with an equal number of individuals above and below the age of 60. LTA‐SMX, LTA‐AC and LTA‐ZNS from 20 patients who previously presented a clinical reaction to one of the drugs and who had a positive LTA result to the specific drug were compared with 20 individuals who received the same drugs but did not present reactions. Binary logistic regression was used to evaluate the statistical significance. Results: In vitro results correlated with the clinical diagnosis. LTA presented a significant difference (P < 0.0001) between control and hypersensitive patients. In each age group, only a single patient had a severe clinical manifestation of SMX‐HSR. These individuals tested positive to both SMX and ZNS. Conclusions: Sulphamethoxazole‐HSR but not AC‐HSR patients may present a cross‐reactivity to ZNS‐HSR. The use of LTA to predict a possible ZNS reaction is recommended for SMX‐sensitive individuals who prescribed ZNS.     

Protective effect of trimethylpsoralen against UV-B erythema

Summary Vitiliginous patients undergoing photochemotherapy with TMP were less susceptible to a sun burn. To investigate this point, the MED for UV-B was measured before, 2 h, and 24 h after oral intake of TMP in 10 healthy volunteers. There was an increase of MED when UV exposure had taken place 2 h after TMP intake (P<0.01). This was no longer detectable when the exposure had taken place 24 h after intake. MED increase was 11.8% for 0.19 mg/kg TMP, 21.0% for 0.37 mg/kg, and 23.7% for 0.74 mg/kg. This dosedependence was significant (P<0.01). The protective effect of TMP against UV-B erythema seemed related to UV absorption by the drug while it was in the blood stream.

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Abbreviations (MED) Minimal Erythemal Dose - (UV-B) Ultra Violet B rays Presented in part at the meeting of the French Dermatological Society, Biological Session, Paris, June 8, 1978This study was supported by a grant of the University of Besançon, Microtechniques Service     

Unusually located lymphocutaneous nocardiosis caused by Nocardia brasiliensis

Summary We report a patient with primary lymphocutaneous Nocardia brasiliensis infection affecting the face and left arm. The mode of infection was via skin abrasions which occurred 2 weeks prior to the development of the skin lesions. Treatment with intravenous minocycline for 4 weeks resulted in a cure. We also review 12 previously reported Japanese cases of lymphocutaneous nocardiosis.     

Scedosporium apiospermum: An unreported cause of fungal sporotrichoid‐like lymphocutaneous infection in Australia and review of the literature

Scedosporium apiospermum is a fungus emerging as a rare but important cause of both localised and disseminated infections in immunocompromised patients. Most cutaneous lesions present as mycetoma, however a review of the literature revealed an increasing number of cases worldwide presenting with lymphocutaneous spread resembling sporotrichosis. An 85‐year‐old man with an extensive medical history including type II diabetes mellitus and meningioma presented with crusted haemorrhagic areas on the dorsum of his left foot and multiple crusted nodules extending proximally along his leg in a sporotrichoid‐like lymphocutaneous pattern. A mycological examination and culture of the cutaneous tissue found the fungus, Scedosporium apiospermum.     

Primary cutaneous nocardiosis in an immune-competent patient.

We present a patient who was hospitalized due to a purulent skin lesion with a surrounding erythematous area in the region of the right paranasal crease accompanied by a swelling of the right eyelid. Initially the diagnosis of a carbuncle caused by an infection with Staphylococcus aureus was supposed. A surgical debridement was performed and an antibiotic therapy was started. Only special microbial investigations requested by the clinician led to the diagnosis of a cutaneous infection with Nocardia brasiliensis. The presented case is remarkable because the nocardia infection was in an immune-competent patient and the patient showed a primary cutaneous nocardiosis without dissemination.     

A single large dose of trimethoprim-sulfamethoxazole fails to cure gonococcal urethritis in men.

In a single-blind study, 50 men who had acute gonococcal urethritis were treated with a single oral dose of either 720 mg trimethoprim (TMP) plus 3,600 mg sulfamethoxazole (SMZ) or 3.5 g ampicillin plus 1 g probenecid. Isolates of Neisseria gonorrhoeae were tested for in-vitro susceptibility to the chemotherapeutic agents administered by agar-dilution and disk-diffusion methods, and results were correlated with cure or failure to cure as determined bacteriologically. Among patients returning for follow up, the cure rate after TMP/SMZ was 69%. Cure was predictable when the isolates of N. gonorrhoeae were inhibited by < or = 0.63/11.87 micrograms/ml of TMP/SMZ (fixed ratio, 1:19) or when the zones of inhibition were > or = 23 mm; failure was predictable when > or = 1.25/23.75 micrograms/ml of TMP/SMZ was necessary for inhibition and when zones of inhibition were < or = 21 mm (P < 0.02). The cure rate after therapy with ampicillin was 100%, a rate significantly higher than that found after TMP/SMZ (P < 0.02); all isolates were inhibited by < or = 0.16 microgram/ml of ampicillin. Adverse reactions were not seen after either TMP/SMZ or ampicillin.