Pulmonary Mycobacterium abscessus infection-induced erythema induratum

Erythema induratum (EI) is clinically characterized by recurrent crops of tender nodules on the lower legs and lobular panniculitis with granulomatous inflammation and pathologically characterized by vasculitis and focal fat necrosis. Currently, many authors consider EI to be a multifactorial disorder with diverse causes, including Mycobacterium tuberculosis and hepatitis C infection. Here, we report a case of a 65-year-old female with a 1-year history of recurrent crops of tender nodules and plaques on her bilateral lower legs. In addition, she had suffered from a chronic cough with sputum for 1 year and had contact history with pulmonary nontuberculous mycobacterial infection from her husband. The histopathological findings of the skin biopsies were consistent with the diagnosis of EI. Chest computed tomography revealed multiple lymphadenopathy and two sets of sputum cultures showed M. abscessus. After 2 months of anti-nontuberculous mycobacterial therapy with ciprofloxacin, the skin lesions resolved completely and there was no recurrence within the following year.     

Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy

Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non‐tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid‐fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation.     

Erythema nodosum-like eruption in sarcoidosis

Two cases of sarcoidosis with tender, erythematous nodules on the legs are reported. The cutaneous lesions were clinically similar to those of erythema nodosum, but histologically showed non-caseating epithelioid granulomas. A review of 14 cases of this particular sarcoid eruption reported in Japan showed that 13 had ocular involvement as in our cases. In the light of the high frequency of ocular involvement, a skin biopsy should be considered in patients presenting with erythema nodosum-like eruptions situated on the legs.     

Histoid leprosy: review of the literature

Leprosy is a chronic granulomatous inflammation primarily of the peripheral nervous system, skin, and reticuloendothelial system caused by Mycobacterium leprae. It presents clinically as an erythematous or hypopigmented anesthetic patch and a thickened and/or tender cutaneous nerve trunk. Leprosy is also called Hansen disease. Leprosy is a great imitator of other skin diseases, and it can present with different morphological lesions, which is why an expert eye is needed to diagnose it. One of the important clinical presentations of leprosy is histoid leprosy, which is very difficult to diagnose due to different clinical and histopathological findings that mimic, e.g., a fibromatous disorder. Histoid leprosy is a very rare clinicopathological variant of leprosy. It is clinically characterized by skin‐colored, soft, succulent nodules, and plaques on apparently normal skin and histologically by a dense bundle of histiocytes arranged in storiform. Though histoid leprosy is a very rare type of leprosy, the higher load of lepra bacilli in these cases makes it a concern as a reservoir for leprosy.     

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.     

Granulomas in acquired immunodeficiency syndrome‐associated cutaneous Kaposi sarcoma: evidence for a role for Mycobacterium tuberculosis

Background: Co‐lesional acquired immunodeficiency syndrome‐associated cutaneous Kaposi sarcoma (AIDS‐KS) and Mycobacterium tuberculosis‐associated granulomatous inflammation are undocumented. Method: Retrospective appraisal of skin biopsies with co‐lesional AIDS‐KS and microscopic tuberculosis (TB). Results: Sixteen biopsies from nine males and seven females form the study cohort. Histological assessment confirmed nodular and plaque KS in 12 and 4 cases each, respectively. Necrotizing, non‐necrotizing and a combination of necrotizing and non‐necrotizing granulomatous inflammation were present in nine, two and five biopsies each, respectively. The identification of acid fast bacilli on Ziehl‐Neelsen staining and M. tuberculosis on polymerase chain reaction confirmed co‐lesional TB in 15/16 biopsies. Co‐lesional AIDS‐KS and lichen scrofulosorum, hitherto undocumented, were confirmed in one biopsy. The histopathological findings served as a marker of human immunodeficiency virus (HIV) infection, visceral TB, therapeutic noncompliance and multidrug resistant pulmonary TB in nine, eight, five and one patient, respectively. M. tuberculosis was cultured from sputum or nodal tissue of all patients. Conclusion: Granulomatous inflammation in KS requires optimal histopathological and molecular investigation to confirm an M. tuberculosis origin. The cutaneous co‐lesional occurrence of AIDS‐KS and microscopic TB may serve as the sentinel clue to HIV infection, systemic TB, therapeutic noncompliance or multidrug resistant TB. Ramdial PK, Sing Y, Subrayan S, Calonje E, Aboobaker J, Sydney C, Sookdeo D, Ramburan A, Madiba TE. Granulomas in acquired immunodeficiency syndrome‐associated cutaneous Kaposi sarcoma: evidence for a role for Mycobacterium tuberculosis.     

Cutaneous non‐tuberculous Mycobacterial infections: a clinical and histopathological study of 17 cases from Lebanon

Background Only a few studies characterized cutaneous non‐tuberculous Mycobacterium (NTM) infections in this region of the world . Objective The aim of this study was to describe the epidemiological, clinical and histological findings of cutaneous NTM infections in Lebanon. Patients/Methods Retrospective study of 17 patients (19 histological specimens) diagnosed with cutaneous NTM infections and confirmed by culture‐based partial sequencing of the 16S rRNA gene at the American University of Beirut Medical Center between 2005 and 2008. Results Of 17 cases, 14 were caused by Mycobacterium marinum. All patients were immunocompetent except for one. Clinically, the most common presentation was multiple sporotrichoid lesions over an extremity (8/17). Many patients had peculiar presentations including bruise‐like patches, herpetiform lesions, annular ulcerated plaques, symmetrical nodules over the buttocks and locally disseminated lesions with surrounding pale halo. Almost all patients cleared their infection on either minocycline or clarithromycin monotherapies. Histologically, a dermal small vessel proliferation with mixed inflammation (granulation tissue‐like changes) was identified in 58% of specimens. The most common type of granulomatous inflammation was the suppurative (47%) followed by the tuberculoid (30%), sarcoidal (11%), and palisading (5%) types. Lichenoid granulomatous dermatitis was noted in 42% of cases. Special staining highlighted mycobacteria in only two specimens. Conclusions The incidence of cutaneous NTM infections is high in our area. Many patients had peculiar clinical presentations. Our study is the second to report the common presence of granulation tissue‐like changes as a good histological indicator of cutaneous NTM infections. Minocycline and clarithromycin remain the drugs of choice in our area.     

Cutaneous infections due to nontuberculous mycobacteria: histopathological review of 28 cases. Comparative study between lesions observed in immunosuppressed patients and normal hosts

To evaluate the histopathological features observed in patients with cutaneous infections due to nontuberculous mycobacteria (NTM) and to compare the histopathological patterns observed in immunosuppressed patients and normal hosts. Twenty-eight biopsy specimens corresponding to 27 patients with cutaneous infections due to NTM were reviewed. Eighteen biopsies corresponded to normal hosts (14 Mycobacterium marinum, 2 Mycobacterium chelonae, 1 Mycobacterium terrae and 1 Mycobacterium gordonae) and 10 biopsy specimens were obtained from 9 immunosuppressed patients (3 Mycobacterium chelonae, one of which had two biopsies, 1 Mycobacterium abscessus, 2 Mycobacterium kansasii, 1 Mycobacterium marinum, 1 Mycobacterium avium complex and 1 Mycobacterium simiae). A panel of histopathological features was evaluated by two independent observers in each biopsy specimen. Epidermal changes (acanthosis, pseudoepitheliomatous hyperplasia, exocytosis) were mainly observed in M. marinum infections. In immunosuppressed patients the infiltrate tended to be deeper, involving the subcutaneous tissue (100%) with a more diffuse distribution and constant abscess formation. A marked granulomatous inflammatory reaction was observed in 83% of immunocompetent and in 60% of immunosuppressed patients. In immunosuppressed patients a relationship between the chronic evolution of the disease and granuloma formation was demonstrated. A diffuse infiltrate of histiocytes with occasionally foamy appearance was noted in three biopsy specimens from three patients with AIDS. Acute and chronic panniculitis was detected in 8 biopsy specimens. In one biopsy (M. chelonae) an acute suppurative folliculitis was observed. Different histopathological patterns can be noted in biopsy specimens from cutaneous nontuberculous mycobacterial infections. The evolution of the disease and the immunologic status of the host may explain this spectrum of morphological changes. Tuberculoid, palisading and sarcoid-like granulomas, a diffuse infiltrate of histiocytic foamy cells, acute and chronic panniculitis, non-specific chronic inflammation, cutaneous abscesses, suppurative granulomas and necrotizing folliculitis can be detected. Suppurative granulomas are the most characteristic feature in skin biopsy specimens from cutaneous NTM infections. Some histopathological patterns seem more prevalent in immunosuppressed patients.     

Mycobacteria other than Mycobacterium tuberculosis are not present in erythema induratum/nodular vasculitis: a case series and literature review of the clinical and histologic findings

Erythema induratum (EI)/nodular vasculitis (NV) is characterized by recurrent crops of tender oedematous nodules on the lower legs. A lobular panniculitis with granulomatous inflammation, vasculitis, focal necrosis and septal fibrosis is present. Mycobacterium tuberculosis DNA has been detected in some lesions by means of polymerase chain reaction (PCR). Ten cases of EI/NV were found. H&E slides were reviewed. PCR assays for M. tuberculosis and mycobacteria other than M. tuberculosis (MOTT) were performed. PCR did not reveal M. tuberculosis (0%) or MOTT (0%) DNA, with positive controls, indicating the reliability of the assays. Among the MOTT, cutaneous infections are most commonly caused by M. marinum. Subcutaneous tuberculoid granulomas may be seen with M. kansasii, M. marinum, M. scrofulaceum and M. avium complex. M. gordonae, M. szulgai and M. malmoense rarely cause cutaneous infections. M. simiae, M. gastri and M. asiaticum are probably not cutaneous pathogens. M. tuberculosis and MOTT DNA was not found in EI/NV. EI/NV has diverse aetiologies with varying pathogeneses leading to similar histologic changes. The cases analysed may not have had an infectious aetiology. However, in EI/NV, performance of PCR for MOTT as well as M. tuberculosis complex may still be beneficial, particularly in cases from immunocompromised hosts.     

Usefulness of Interferon-γ release assays in the diagnosis of erythema induratum

BACKGROUND: Erythema induratum (EI) manifests as tender indurated nodules on the lower legs. It may be associated with concomitant active tuberculosis (TB) and is considered a hypersensitivity reaction to mycobacterial antigens. However, the results of Mycobacterium cultures are rarely positive, and the tuberculin skin test is of limited usefulness in populations exposed to bacille Calmette-Guérin (BCG). Interferon-γ release assays (IGRAs) are alternatives to the tuberculin skin test and have high specificity. We explored the use of IGRAs as an adjunct in the diagnosis of EI. We describe 5 patients with positive tuberculin skin test results and a history of vaccination against BCG or TB in whom IGRAs supported the diagnosis of EI. OBSERVATIONS: All patients were initially seen with tender nodules on the lower legs and a history of BCG vaccination or TB. Tuberculin skin test results were positive, and chest radiographic results were normal. The results of Mycobacterium cultures were negative in all patients, and biopsy specimens were compatible with EI. Interferon-γ release assays were performed in all patients and supported initiation of anti-TB treatment in 4 of 5 patients. Conclusion Interferon-γ release assays may have value as an adjunct in the diagnosis of EI, particularly in the setting of prior BCG exposure.     

Disseminated cutaneous Mycobacterium kansasii infection presenting with Rosai–Dorfman disease‐like histological features in a patient carrying anti‐interferon‐γ autoantibodies

Typical cutaneous non‐tuberculous mycobacteria (NTM) infections show a histopathology pattern of granulomas with admixed Langhans giant cells, and abscesses may be observed in acute lesions. Herein, we describe a patient carrying a high titer of autoantibodies to interferon (IFN)‐γ with disseminated Mycobacterium kansasii infection presenting with emperipolesis and Rosai–Dorfman disease (RDD)‐like histopathological features characterized by remarkable, large, pale‐staining “RD cells”, which were CD68 and S100 positive and CD1a negative. The patient was misdiagnosed with RDD initially, but exhibited a poor response to all interventions. A re‐biopsy revealed Langhans‐type multinucleated giant cells; multiple definite acid‐fast bacilli were also found. M. kansasii was isolated from cultured tissues. Anti‐NTM treatment was initiated. After treatment, all lesions resolved almost completely within the following month. High‐titer anti‐IFN‐γ autoantibodies were detected during follow up, leading to the diagnosis of adult‐onset immunodeficiency syndrome. In conclusion, patients carrying high‐titer autoantibodies to IFN‐γ who also have a disseminated cutaneous M. kansasii infection may present with RDD‐like histopathological features, which may be a pitfall in the diagnosis of disseminated cutaneous NTM infections.     

WIDESPREAD PRIMARY CUTANEOUS INFECTION WITH MYCOBACTERIUM FORTUITUM

Background. Cutaneous infection with Mycobacterium fortuitum, a ubiquitous rapid growing atypical mycobacterium, most often occurs as a postsurgical wound complication or at the site of a penetrating injury to the skin. Rarely, disseminated infection with cutaneous involvement can occur in immunocompromised patients. Case Report. A 47-year-old black woman presented with a 10-year history of numerous draining abscesses and tender nodules on the back and buttocks unresponsive to oral and intravenous antibiotics. Biopsy showed a granulomatous and suppurative dermatitis and panniculitis and special stains did not reveal organisms. M. fortuitum was cultured from involved skin on two separate occasions. The patient improved with a 2-week course of intravenous amikacin and cefoxitin combined with oral probenecid followed by a course of doxycycline and ciprofloxacin. Conclusions. Widespread primary cutaneous infection with M. fortuitum may occur in an immunocompetent patient. Chronic draining skin abscesses unresponsive to routine antibiotics may represent infection with an atypical mycobacterium; tissue cultures of affected skin should be performed to rule out this possibility. Therapy should be directed by culture sensitivity results.     

Wrong diagnosis erysipelas: hypodermitis – case series and review of literature

Background: Patients with an advanced chronic venous insufficiency (CVI) often show inflammatory changes of their legs. Often erysipelas is diagnosed and systemic antibiotic therapy initiated. Frequently this approach is not successful. Patients and Methods: During the last 6 months 5 patients with an outside diagnosis of erysipelas presented to our clinic. All had a painful erythema of the medial part of one or both calves and all failed numerous antibiotic regimens. Results: In all patients a sharply demarcated, tender indurated erythema of the medial part of one or both calves was seen. Inguinal lymphadenopathy, fever and other systemic signs and symptoms were absent. In 4 of 5 patients normal laboratory inflammatory parameters were normal. We diagnosed hypodermitis in all. They were treated with compression therapy and topical corticosteroids. In addition, their underlying CVI was addressed. Conclusions: Dermatosclerosis is often seen in patients with advanced CVI. An acute inflammatory phase (hypodermitis) and a chronic phase of the disease can be differentiated. The acute hypodermitis can imitate erysipelas clinically, with systemic signs and symptoms, as well as laboratory evidence of inflammation generally being absent.     

Cutaneous manifestations of Takayasu arteritis. A retrospective study of 80 cases

The aim of this retrospective study is to delineate in Europe the frequency and type of cutaneous manifestations associated with Takayasu arteritis (TA). Eighty patients with TA were analyzed. Symptoms suggestive of Raynaud's syndrome were noted in 11 patients (14%) and could be directly related to large vessel involvement. Other skin lesions were observed in 10 patients (12.5%). Five had acute tender erythematous nodules on the legs with a clinical diagnosis of erythema nodosum; 2 had subacute ulcerated nodules of the legs; 1 had pyoderma-gangrenosum-like ulcerations of the four limbs which resulted from the breakdown of subcutaneous nodules; 1 had lupus-like malar flush, and the last one had urticarial lesions with livedo reticularis. Skin samples were obtained from 4 patients. Three of them agreed that reiterated biopsies be done on recurrent lesions. A granulomatous vasculitis was observed in 2 cases involving hypodermal arterioles in one case and veins in the other. The other pathological findings were septal and lobular panniculitis which can be associated with granulomatous vasculitis. Different histological findings on reiterated biopsies were frequently found. The absence of any other etiology and chronological arguments suggested a relationship between these skin lesions and TA. Tuberculosis was probable in 1 case but apparently was not related to the skin lesions.     

A Pediatric Case of Atypical Mycobacterium avium Infection of the Skin

We report a case of cutaneous atypical mycobacteriosis in a 12-year-old healthy girl due to Mycobacterium avium. The cutaneous symptoms were three well-defined subcutaneous nodules on both buttocks and on the posterior surface of the left thigh. One had a fistulous opening on the skin surface. Histopathological examination revealed epithelioid cell granulomas surrounded by dense lymphocytic infiltration and acid-fast bacteria were seen with modified periodic acid-carbol fuchsin staining. Using Ogawa's medium at 37°C, acid-fast bacteria were isolated from the biopsied specimen and identified by the DNA-DNA hybridization method as Mycobacterium avium. In drug susceptibility test, these were resistant to all antituberculous drugs. Oral administration of minocycline 100 mg/day for two months had little effect on the two remaining lesions, which were therefore excised. Based upon reported cases of Mycobacterium avium complex, we considered that our pediatric patient with multiple intradermal or subcutaneous nodules on the buttocks and the thigh exhibited the characteristic symptoms of M. avium infection.     

ERYTHEMA INDURATUM OE BAZIN

Background. There has been a long controversy about the tuberculous cause of erythema induratum, a chronic form of nodular vasculitis. Method. We investigated clinical, histopathologic, and immunohistochemical features of patients with erythema induratum who showed positive tuberculin hypersensitivity reactions or had associated active tuberculosis. Results. The ages of the 32 patients (M 7: W 25) ranged from 13 to 66 years (mean 36.6 years). All patients displayed recurrent crops of tender, painful, violaceous nodules or plaques. Most lesions presented on the legs, but they also occurred on thighs, feet, buttocks, and forearms. The skin lesions evolved for several weeks and healed with scarring and residual pigmentation. Twenty-two patients were treated with isoniazid alone and the remaining 10 patients received combinations of antituberculous drugs. Relapses were encountered in four patients who received isoniazid alone or stopped the medication against medical advice. In most biopsies, histologic examination revealed lobular or septolobular panniculitis with varying combinations of granulomatous inflammation, primary vasculitis, and necrosis. Immunohistochemical labeling revealed a preponderance of T lymphocytes, monocyte-macrophages, and Langerhans' cells, indicative of a type IV hypersensitivity reaction. Conclusion. Erythema induratum of Bazin has distinct clinical, histopathologic, and immunohistochemical features. Erythema induratum of Bazin should be considered as a separate entity of nodular vasculitis caused by latent foci of tuberculous infection.     

Linfoma cutáneo primario difuso de células grandes-tipo pierna con regresión espontánea

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy.We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature.     

Treatment of Mycobacterium haemophilum infection with an antibiotic regimen including clarithromycin

A patient with rheumatoid arthritis developed ulcerated nodules predominantly on his legs. Skin biopsy and culture demonstrated rheumatoid vasculitis and infection with Mycobacterium haemophilum. Improvement was not seen until clarithromycin was added to his treatment regimen.     

皮肤嗜血分枝杆菌感染二例研究

目的 提高对皮肤嗜血分枝杆菌感染的认识。 方法 报道2例皮肤嗜血分枝杆菌感染的临床表现、组织病理、病原学特点及治疗随访的情况。 结果 2例患者均存在免疫功能低下,皮损均发生在外伤后,临床最初均表现为界限清楚的皮下结节,逐渐出现破溃结痂和脓肿形成。组织病理显示真皮内上皮细胞肉芽肿形成或组织细胞浸润,伴有灶状坏死和中性粒细胞脓肿形成。抗酸染色可见大量的阳性杆菌。细菌仅能在含有铁离子的培养基中生长,病原体经PCR后测序符合嗜血分枝杆菌。根据药敏结果,给予患者利福平、克拉霉素和莫西沙星联合治疗后3个月,病情好转。 结论 嗜血分枝杆菌感染常发生于免疫抑制人群中,继发于外伤,表现为皮下结节和脓肿,组织学符合感染性肉芽肿改变,分子生物学是鉴定本病的可靠方法。     

Cutaneous melioidosis with unusual histological features

Melioidosis is caused by the saprophytic gram‐negative bacillus Burkholderia pseudomallei, and has varied presentations, with cutaneous manifestations occurring in about 13% of cases. The usual histopathological features of melioidosis are suppurative to chronic granulomatous inflammation. Recommended treatment of melioidosis is sequential use of intravenous followed by oral antibiotics for a few months, although oral antibiotics alone can be used in primary cutaneous melioidosis. We report a case of cutaneous melioidosis in a healthy young man, with the unusual histopathological feature of lymphoplasmacytic inflammation, and failing an initial trial of oral antibiotics alone.