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.     

Erythema induratum in a patient with active tuberculosis of the axillary lymph node: IFN-gamma release of specific T cells

A 57-year-old woman with tender nodular lesions on her legs, arms, buttocks and face is reported as a case of erythema induratum (EI) with active tuberculosis of axillary lymph nodes. Both skin nodular lesions and lymph nodes responded positively to antituberculous therapy. The patient's peripheral blood mononuclear cells showed a high proliferation and produced interferon-gamma (IFN-gamma) in response to purified protein derivative (PPD). These findings indicate the possibility that PPD-specific T cells, capable of producing IFN-gamma, are likely to be involved in the formation of EI as a type of delayed-type hypersensitivity response to mycobacterial antigens at the site of skin lesions.     

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.     

Skin infection caused by Mycobacterium avium

A patient with skin infection due to Mycobacterium avium is reported. A 9–year–old female had 10 subcutaneous nodules and two ulcers on the abdomen and legs. She had no medical history of systemic disease, skin disease or immunosuppressive therapy. Cultures of a biopsy specimen and of aspirated seropurulent fluid in nodules showed acid–fast bacteria, identified as M. avium by the DNA–DNA hybridization method. We treated her with a combination of surgery and the antibiotics, cycloserine, isoniazid and clarithromycin.     

The fish tank strikes again: Metachronous nontuberculous mycobacterial skin infection in an immunosuppressed host

An 82‐year‐old woman on long‐term prednisolone for chronic obstructive airways disease presented with a 2‐month history of nodules on her left forearm. This occurred 10 years after nodules on her right forearm caused by a culture‐proven Mycobacterium marinum infection. Histopathological examination, polymerase chain reaction and culture of biopsy specimens were positive for M. chelonae. To our knowledge this is the first case of metachronous nontuberculous mycobacterial skin infection reported, and it highlights the diagnostic and therapeutic challenges of such infections.     

Heterozygous prothrombin gene mutation associated with livedoid vasculopathy

A 53-year-old woman presented with a chronic history of recurrent, painful ulcers, predominantly involving her lower legs. Both her clinical picture and histopathological findings were consistent with a diagnosis of livedoid vasculopathy, although she did have unusual findings of deep tender nodules and the presence of lesions over her elbows. Multiple investigations were undertaken, the only abnormality being a heterozygous mutation of the prothrombin G2021A gene. Although various coagulopathic states have been associated with livedoid vasculopathy, the finding of an associated prothrombin gene mutation is quite rare. Warfarin has ameliorated the clinical course when anti-inflammatory drugs and other anticoagulants were unhelpful.     

Successful treatment of lymphomatoid papulosis with photodynamic therapy

A 40-year-old woman presented with a prolonged history of recurrent crops of erythematous papules and nodules on her abdomen, arms and legs. Histological examination of a cutaneous biopsy revealed Type A lymphomatoid papulosis. Over a 3-year period, some of the patient's lesions had proven to be resistant to treatment with topical and intralesional corticosteroids and systemic agents including methotrexate, tetracycline and nicotinamide. These resistant lesions were treated with two sessions of methyl aminolevulinate photodynamic therapy given 1 week apart. Review 11 months post-photodynamic therapy demonstrated complete clinical clearance at the treatment site. While photodynamic therapy is considered a standard non-surgical treatment option for non-melanoma skin cancers and has been described in a number of non-oncological indications, this is the first report of its use in lymphomatoid papulosis.     

Cutaneous polyarteritis nodosa: a report of a case associated with melioidosis (Burkholderia pseudomallei)

A 22-year-old Thai woman was hospitalized with a 1-month history of high-grade fever and slowly progressing multiple erythematous painful nodules on both legs. A history of arthralgia in the knee and ankle joints was presented. She had been treated with acetaminophen and a non-steroidal anti-inflammatory drug (NSAID) from a provincial hospital before, but without improvement. She denied the histories of upper respiratory tract infection, jaundice, tuberculosis, and taking any drugs before skin eruption. On physical examination, she had a temperature of 40 °C, a pulse rate of 90 beats per minute, a respiratory rate of 22 breaths per minute, and a blood pressure of 110/60 mmHg. She had multiple 1–4 cm erythematous, oval, tender, nodules on the pretibial area of both legs. Some nodules also had fluctuation and hemorrhagic bullae ( Fig. 1 ). Other physical examinations were normal, except for positive splenic dullness on percussion.

Figure 1 Open in figure viewer PowerPoint Erythematous, subcutaneous nodules with hemorrhagic bleb on both legs     

Rheumatoid neutrophilic dermatitis in a woman with seronegative rheumatoid arthritis

Rheumatoid neutrophilic dermatitis (RND) is an unusual cutaneous reaction in patients with rheumatoid arthritis (RA). RND is characterized by symmetric, erythematous papules, plaques, nodules, and urticarial lesions often located over the joints, extensor surfaces of the extremities, or the trunk. This entity demonstrates an intense neutrophilic dermal infiltrate without vasculitis. All patients previously reported with RND had severe RA with relatively high titers of rheumatoid factor when tested. A 67-year-old woman had a 2-month history of multiple, tender, 4 to 8 mm erythematous, crusted papules and nodules that occurred in clusters on her anterior thighs, knees, and legs. She suffered from severe disabling seronegative RA. RND may complicate seronegative RA.     

Nephrogenic systemic fibrosis in a gadolinium-naive renal transplant recipient

A 36-year-old woman presented with a 2-year history of multiple, raised, brown papules and indurated skin over her lower legs. She had received a renal transplant 11 years earlier, and had a history of recurrent deep vein thromboses despite a negative thrombophilic screen. The patient had no history of exposure to gadolinium. Histology at this time revealed a light perivascular lymphoid infiltrate, activated fibroblasts and prominent capillary vessels. The patient re-presented 1 year later with persistence of these lesions, in the setting of worsening renal function requiring haemodialysis. Repeat skin biopsies demonstrated increased dermal collagen and angiogenesis. The dermatopathological findings, in association with renal insufficiency and multiple deep vein thromboses, led to the diagnosis of nephrogenic systemic fibrosis.     

Erythema induratum (nodular vasculitis) associated with Crohn's disease: a rare type of metastatic Crohn's disease

We herein report a patient with erythema induratum/nodular vasculitis (EI/NV) associated with Crohn's disease (CD), which is considered to be a rare type of metastatic CD. A 54-year-old woman, who had a history of CD, presented with erythematous nodules on her legs. The histopathological features of the skin biopsy revealed a granulomatous, mixed septal and lobular panniculitis, which was characterized by many discrete epithelioid cell granulomas (necrobiotic/necrotizing-type and sarcoidal type), necrosis of the adipocytes, and granulomatous phlebitis in the muscular wall of a subcutaneous vein. A review of the pertinent literature and the presented case suggested the following: (1) panniculitis associated with CD may be either an erythema nodosum type or an EI/NV type; (2) so far, the reported cases of metastatic CD or granulomatous vasculitis in CD rarely presented with granulomatous panniculitis without dermal involvement, and most cases showed histopathological features that were similar to or indistinguishable from those of EI/NV; and (3) the finding of granulomatous vasculitis (especially the presence of discrete epithelioid cell granulomas involving the veins or venules) may be a characteristic feature of EI/NV associated with CD, in contrast to the finding of acute vasculitis, which is typically present in patients with EI/NV due to causative factors other than CD.     

Acute onset of neutrophilic dermatosis in patients after therapy with a COX-2-specific inhibitor

Case 1 A 31‐year‐old black woman with an 8‐year history of Crohn's disease (CD) presented with multiple, erythematous, tender, leg nodules. She had started to develop these areas approximately 2 weeks earlier. About 1 week prior to the development of these areas, the patient had gone to her primary care physician because of increasing joint pains. She was given rofecoxib, 50 mg/day. A few months earlier, the patient had stopped taking the medication that had been prescribed for CD: sulfasalazine and prednisone. Since stopping sulfasalazine and prednisone, her gastrointestinal symptoms had increased. After starting rofecoxib, the patient did not notice any significant change in her gastrointestinal symptoms, although her arthritic symptoms improved. Earlier on the day of presentation, the patient's gastroenterologist had instructed her to stop rofecoxib, and to re‐start sulfasalazine and prednisone. On physical examination, the patient had multiple erythematous nodules on both legs, predominantly on the lower legs anteriorly and posteriorly ( Fig. 1a ). Some of the nodules showed central pustules and some showed superficial epidermal ulceration ( Fig. 1b ). A biopsy was performed on an indurated lesion that had not yet ulcerated.

Figure 1 Open in figure viewer PowerPoint Multiple, erythematous nodules on the legs of a patient with Crohn's disease (Case 1). Biopsy specimens from some lesions showed subepidermal pustule formation with or without epidermal ulceration     

PANCREATIC PANNICULITIS IN A CHILD

Pancreatic panniculitis is an uncommon cause of panniculitis. It is associated with acute or chronic pancreatic disease. 1½ year old boy was referred for erythematous tender nodules involving both legs and associated with abdominal distention, fever, and vomiting. Dermatological examination revealed multiple erythematous tender nodules distributed over front and back of legs. Blood chemistry showed raised serum amylase (430 IU/ 1). Ultrasonography showed a pseudopancreatic cyst. Multislice CT scan was suggestive of a pseudopancreatic cyst. A skin biopsy showed typical features of pancreatic panniculitis which included lobular panniculitis with lipocyte degeneration with few Ghost cells.     

Skin lesions serve as clues to relapse of pediatric blastic plasmacytoid dendritic cell neoplasm

A 10‐year‐old girl with a history of blastic plasmacytoid dendritic cell neoplasm, a rare malignancy in children, presented with recurrent skin eruptions beginning while on maintenance chemotherapy, including mildly pruritic skin‐colored plaques, tender indurated nodules, and violaceous bound‐down plaques. This case highlights an unusual presentation of relapsed blastic plasmacytoid dendritic cell neoplasm on chemotherapy, with skin lesions providing important clues to the progression of systemic disease.     

A Case of Skin and Soft Tissue Infection Caused by Mycobacterium abscessus

Mycobacterium abscessus (M. abscessus) is an acid-fast bacillus that''s classified as a pathogenic "rapid growing" nontuberculous mycobacteria. It is an uncommon cause of human disease, but it can cause skin and soft tissue infection after skin injury following inoculation, minor trauma and surgery. The single most important factor for determining the course and prognosis of a M. abscessus infection is the underlying immune status of the host. We report here on a 71-year-old female who presented with multiple painful erythematous cutaneous nodules on her left forearm. She had diabetes mellitus and had taken oral steroid by herself for two years because of her osteoarthritis. Histologically, granulomas and inflammatory cell infiltration were observed and M. abscessus was identified via the mycobacterial culture. We performed curettage and drainage, followed by 6 months of oral clarithromycin and the patient''s disease completely healed.     

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.     

坏疽性脓皮病合并无菌性肺脓肿及类风湿性关节炎1例

报告1例坏疽性脓皮病合并无菌性肺脓肿及类风湿性关节炎。患者女，65岁。小腿反复破溃2年，加重20d人院。既往有类风湿性关节炎10余年。入院查胸部CT示双肺多发性结节空洞．肺结节穿刺抽出灰黄色脓性液体，脓液未查到病原菌。给予皮质类固醇治疗，皮损及肺部病变均有好转。     

Panniculitis with pseudomonas septicaemia in AIDS

A 27 year old female with acquired immunodeficiency syndrome (AIDS) developed tender erythematous nodules on her thighs. A skin biopsy of the lesions showed septal panniculitis and venulitis and Pseudomonas species was cultured from both the urine and the skin biopsy tissue. The lesions resolved on antibiotic therapy. Panniculitic nodules may represent an early stage of ecthyma gangrenosum which is a well recognised cutaneous complication of pseudomonas septicaemia.     

Tender cutaneous nodules of the legs: diagnosis and clinical clues to diagnosis

Background “Tender cutaneous nodules of the legs” is a common manifestation in dermatology. Histopathological investigation is usually required for this condition, because clinical data are frequently insufficient to make a definite diagnosis. Objective To identify and analyze the causes of patients presenting with tender leg nodules and to reveal clinical clues that could help to differentiate causes. Materials and methods The medical records and histopathological slides of patients presenting with tender cutaneous nodules of the legs between January 2005 and December 2007 were retrospectively reviewed. Results  Of the total of 154 patients, 122 (79.2%) were female. Definite diagnoses were categorized into four groups: inflammation (84.4%); infection (5.8%); tumor (6.5%); and nonspecific (3.2%). The most common cause in the inflammation group was erythema nodosum. The infections found were Acremonium spp., Penicillium sp., Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium leprae. The tumors included leiomyoma, leukemia cutis, and lymphomas. Clinical data that correlated with and could be used as clues for the inflammation group were female sex (P = 0.03, OR 6.43) and lower leg involvement (P = 0.03, OR 7.14). Limitations The retrospective manner of this study is a limitation. Conclusion Various inflammatory conditions, infections, and tumors can present as tender cutaneous nodules of the legs. Female sex and lower leg involvement were clinical data that could be used as clues for the diagnoses in the inflammation group. However, histopathological investigation is still crucial to determine a definite diagnosis in patients presenting with tender cutaneous nodules of the legs.     

Sporotrichoid Mycobacterium marinum infection of the face following a cat scratch

Mycobacterium marinum infections in humans uncommonly affect the face and are not known to be associated with cat scratches. We describe a 24-year-old woman who presented with a 3-month history of multiple tender, occasionally discharging cystic nodules involving the left side of her face in a sporotrichoid distribution. She had suffered a cat scratch to her left lower eyelid 3 weeks before the onset of the eruption and owned multiple tropical fish tanks. She was systemically well and had no lymphadenopathy. She had a background history of a 4.5-mm-thick nodular melanoma of her temple treated by wide local excision and negative sentinel lymph node biopsy 4 years prior. Skin biopsies showed multiple variably sized granulomas surrounded by thick cuffs of lymphocytes involving the superficial and deep dermis with no organisms seen on Ziehl–Neelsen, peroidic acid-Schiff and methenamine silver stains. Laboratory investigations showed a mildly raised erythrocyte sedimentation rate but normal full blood count and C-reactive protein. Fluid from the left cheek grew an acid-fast bacillus identified as Mycobacterium marinum . The skin eruption cleared after 5-month treatment with oral clarithromycin 500 mg twice daily and rifampicin 600 mg daily.