Nodular tuberculid: a report of four patients

The tuberculids are hypersensitivity reactions to Mycobacterium tuberculosis (MTB) and include papulonecrotic tuberculid (PNT), lichen scrofulosorum, erythema induratum of Bazin (EIB), and phlebitic tuberculid. Papulonecrotic tuberculid displays papulonecrotic lesions mostly on the extensor surfaces of the limbs. Histopathology shows necrosis, granulomatous inflammation (GI), and occasionally vasculitis, usually in the superficial dermis. Erythema induratum of Bazin shows nodulo-ulcerative lesions on the posterior aspect of the legs. Histopathology reveals a septolobular panniculitis, necrosis, GI, and vasculitis. The Mantoux test is strongly positive and associated tuberculosis (TB) may be present in both conditions. MTB cannot be demonstrated with a Ziehl-Neelsen (ZN) stain or cultured. The polymerase chain reaction has demonstrated MTB DNA in PNT (50%) and EIB (25%). The tuberculids respond to full anti-TB treatment. We document four patients with nodules on the legs in whom the pathologic changes were situated in the deep dermis and adjacent subcutaneous fat. Nodular tuberculid (NT) is regarded as a suitable term for these lesions. All patients were female. Their ages were 19 months, 12 years, 17 years, and 5 years. All patients presented with nodules on the limbs. These nodules were approximately 1 cm in diameter, dull red or bluish-red, and nontender. Ulceration was not present. The number of nodules varied from a few to many. The Mantoux test was strongly positive in all the patients. Associated pulmonary TB was present in two patients. Histopathology showed GI (n = 4), vasculitis (n = 2), and coagulative necrosis (n = 2). A ZN stain was negative in each case. All patients received anti-TB treatment for 6 months [rifampicin (n = 4), isoniazid (n = 4), pyrazinamide (n = 4), and ethambutol (n = 2)]. At 12 months follow-up, skin and pulmonary lesions had resolved in all. Nodular tuberculid should be distinguished from arthropod bites and papular urticaria, dermal erythema multiforme, evolving vasculitis, evolving folliculitis, and erythema nodosum. Histopathologically NT should be distinguished from other causes of granulomatous vasculitis and GI with or without necrosis. In children with nodules on the limbs unresponsive to routine treatment, skin biopsy should be done to exclude NT. Nodular tuberculid represents a hybrid between PNT and EIB with characteristic clinicopathologic features and should be included in the classification of cutaneous TB.     

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.     

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.     

Annular lesions of cutaneous sarcoidosis with granulomatous vasculitis

Sarcoidosis is known to be involved in diseases with vasculitis as sarcoid vasculitis. However, vasculitis in cutaneous sarcoidal lesions is extremely rare. Here we describe a case of sarcoidosis with multiple annular skin lesions with granulomatous vasculitis. A 62‐year‐old female was diagnosed with sarcoidosis by chest‐abdominal computed tomographic examination and laboratory tests. The skin lesions had appeared on her lower limbs 2 years before. Physical examination showed multiple infiltrated annular eruptions on the lower extremities. A skin biopsy of an area of erythema showed multiple non‐caseating epithelioid cell granulomas in the dermis and subcutaneous fat and granulomatous vasculitis with fibrinoid degeneration in the subcutaneous fat. There are two types of vasculitis in sarcoidosis: leukocytoclastic and granulomatous vasculitis. Ulcers and livedo were more common in granulomatous vasculitis than in leukocytoclastic vasculitis. The present case had unique annular skin lesions of sarcoidosis with granulomatous vasculitis.     

Cutaneous manifestations of Takayasu's arteritis. A clinicopathologic correlation

Takayasu's arteritis is a chronic, granulomatous, large-vessel arteriopathy of unknown cause. We retrospectively reviewed the medical records of 38 patients with Takayasu's arteritis and identified 21 with cutaneous findings. Seven patients had lesions that were related to their systemic vasculitis. We found a Churg-Strauss granuloma, a pyodermatous leg ulcer, and inflammatory leg nodules in these patients. Biopsy specimens from three patients with presumed "erythema nodosum" did not support the clinical diagnosis but did show arteritis. In patients with Takayasu's arteritis, small-vessel inflammation, and other inflammatory lesions may be present, in addition to large-vessel disease. Histopathologic study is necessary to categorize the nature of inflammatory leg nodules of these patients.     

Granulomatous arteritis in cutaneous lesions of Churg-Strauss syndrome

BACKGROUND: Although granulomatous arteritis is usually found in extracutaneous Churg-Strauss syndrome (CSS) lesions, the vasculitis in CSS cutaneous lesions typically shows small vessel vasculitis (leukocytoclastic vasculitis) without demonstrating the feature of granulomatous arteritis confirming the proper classification of CSS in the category of granulomatous vasculitis. METHODS: Four deep excisional biopsies were obtained from three untreated CSS patients who presented with livedo reticularis and subcutaneous nodules. Tissue blocks were recut and submitted for hematoxylin and eosin and elastic tissue staining to evaluate the histological features of the affected vessels. Immunostaining for histiocytes, lymphocytes, and neutrophils were performed on serial sections to confirm the cellular infiltration. RESULTS: In all specimens, subcutaneous granulomatous arteritis was observed. The unique histological feature distinct from other vasculitic disorders is characterized by marked infiltration of histiocytes and multinucleated giant cells in and around the disrupted subcutaneous arterial walls mixed with an eosinophilic infiltrate. In two specimens, granulomatous arteritis was found in the subsequent serial sections, not in the initial sections. The initial section may show extravascular granulomatous inflammation without evidence of vasculitis. CONCLUSIONS: Granulomatous arteritis as identified in the extracutaneous lesions can also be found in subcutaneous CSS lesions presenting with livedo reticularis and/or subcutaneous nodules.     

Cutaneous granulomatous vasculitis: its relationship to systemic disease

Microscopic and medical review of twenty-six patients with skin biopsy specimens that showed granulomatous vasculitis demonstrated vascular histiocytic granulomas with fibrinoid destruction of blood vessels in the dermis and panniculus. Cultures of the biopsy specimens were nonspecific. The skin lesions varied from erythema to papulonodular and vesicular eruptions; they were usually on the extremities but also involved the trunk. Eight patients had systemic lymphoproliferative diseases: three, lymphoma; two, angioimmunoblastic lymphadenopathy; two, preleukemia; and one, chronic granulocytic leukemia. Five of these eight patients died within 2 years after the onset of skin lesions. The four patients with systemic vasculitis died within 1 year after the onset of skin lesions. Five patients with arthritis, four with gastrointestinal disease, three with systemic sarcoidosis or sarcoidlike disease, and one with tuberculosis had a more favorable prognosis. The histologic pattern of cutaneous nonlymphomatoid granulomatous vasculitis is associated with significant systemic disease, especially lymphoproliferative disorders. Patients with lymphoproliferative disorders or systemic vasculitis have a much poorer prognosis than those with inflammatory or infectious granulomatous disease.     

Palisaded neutrophilic and granulomatous dermatitis in association with sarcoidosis

Palisaded and neutrophilic granulomatous dermatitis (PNGD) has been associated with many conditions including rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, and other diseases with circulating immune complexes. Lymphoproliferative conditions, bacterial endocarditis, and various drugs can also induce this condition. Many patients also have symmetric polyarthritis with various serological abnormalities. We present a case of a 46‐year‐old female who presented with painful erythematous annular plaques and nodules on her legs. The lesions started a week prior to visit and increased in number over the course of the week. The patient had an established history of sarcoidosis with past episodes of uveitis and erythema nodosum. The histopathological findings included a diffuse pandermal infiltrate mostly composed of neutrophils, nuclear debris, and strands of deeply eosinophilic degenerated collagen. Vasculitis was not present. No significant increase in dermal mucin was detected. Based on the clinical and pathological findings, the patient was diagnosed with late‐stage PNGD. To our knowledge, this is the first case of PNGD described in an adult patient of sarcoidosis. Mahmoodi M, Ahmad A, Bansal C, Cusack CA. Palisaded neutrophilic and granulomatous dermatitis in association with sarcoidosis.     

Cutaneous manifestations of Wegener granulomatosis.

In a series of 19 patients (15 male and 4 female) who had Wegener granulomatosis with specific cutaneous histopathologic findings, the skin was only involved at onset in two. Four distinct histologic subgroups were defined as follows: necrotizing vasculitis (11 patients); necrotizing palisading granuloma (Churg-Strauss lesion) 2 patients); granulomatous vasculitis (2 patients); and lymphomatoid granulomatosis (4 patients). The 11 patients with necrotizing vasculitis had purpuric and hemorrhagic lesions, and the presence of vesicles and ulceration correlated with the severity of onset and extent of disease. The remaining eight patients had papular and nodular lesions. The patients with necrotizing vasculitis and lymphomatoid granulomatosis had a worse prognosis that did those with a predominant granulomatous reaction.     

Nodular granulomatous phlebitis: a phlebitic tuberculid

A 22-year-old woman presented with recurrent non-ulcerating skin nodules overlying the great saphenous vein on the anteromedial lower legs. Histology showed a granulomatous phlebitis, and polymerase chain reaction performed on lesional skin detected DNA specific for Mycobacterium tuberculosis. The lesions resolved with anti-tuberculous therapy. This case may be a further example of nodular granulomatous phlebitis, a phlebitic tuberculid.     

伴Kasabach-Merritt现象卡波西形血管内皮瘤和丛状血管瘤的临床及病理特征

目的 探讨伴Kasabach-Merritt现象(KMP)的卡波西形血管内皮瘤(KHE)和丛状血管瘤(TA)临床病理特征.方法 对7例伴KMP的KHE和TA病例进行临床及病理学分析.结果 诊断为KHE 5例,TA 2例,均伴有血小板降低.7例均在出生后1月内发病,病灶均位于躯干或四肢.2例快速增大,2例缓慢进展,3例稳定或逐渐消退.二者病灶外观多样,典型表现为暗红或紫红色肿块或斑片.组织学上,KHE和TA均由结节状梭形血管内皮细胞团构成.区别在于KHE内皮细胞团边界不清,红细胞淤滞,含铁血黄素沉积;TA内皮细胞团界限清晰,呈弹坑样分布.口服泼尼松治疗2例,切除植皮1例,效果满意;随访观察4例,病情无进展.结论 KMP病理性质为KHE或TA,前者为中间性肿瘤,具局部侵袭性,后者为良性肿瘤,二者均可部分白行退化,需与其他类型血管性肿瘤鉴别.     

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.     

Granuloma annulare with a mycosis fungoides-like distribution and palisaded granulomas of CD68-positive histiocytes

We describe 3 unusual cases of granuloma annulare with multiple macular lesions in a distribution that simulated mycosis fungoides in patients with no associated underlying diseases. Repeated biopsies showed typical well-formed palisading granulomas and no evidence of an atypical lymphocytic infiltrate. There was no vasculitis, neutrophilic, eosinophilic, or interstitial infiltrate. The patients had no associated underlying diseases. Most of the histiocytes in the palisading granulomas were strongly positive for CD68. The lymphocytes were a minor component of the granulomatous inflammation and were predominantly CD8(+) T-cells. The findings in these cases add to the spectrum of previously defined granulomatous eruptions of the skin.     

Takayasu's disease with cutaneous involvement

Takayasu's arteritis (TA) is a chronic inflammatory and fibrosing arteriopathy that can also involve cutaneous vessels. The disease typically presents with a prepulseless phase that overlaps or is followed by the characteristic pulseless stage. In both phases of TA, cutaneous manifestations may be present. Lesions considered to be 'specifically' associated with TA have been described most frequently simulating erythema nodosum, erythema induratum and pyoderma gangrenosum. We report 2 Caucasian patients with TA and nodular cutaneous lesions. Nine skin biopsies from these patients were studied. A necrotizing vasculitis was present in 5 biopsies. We review those patients with TA and well-documented cutaneous manifestations in the English literature, with special interest in nodular lesions, the most frequent cutaneous manifestation of TA in Caucasian patients. Biopsies from lesions with similar morphology frequently show different histological findings.     

Sterile neutrophilic folliculitis with perifollicular vasculopathy: a distinctive cutaneous reaction pattern reflecting systemic disease

The authors prospectively encountered skin biopsies from 20 patients which demonstrated a neutrophilic or suppurative and granulomatous folliculitis accompanied by a folliculocentric neutrophilic vascular reaction of Sweet's-like or leukocytoclastic vasculitis subtypes. While in each case the histomorphology raised diagnostic consideration of bacterial folliculitis, patients frequently expressed systemic complaints such as arthritis, fever, and malaise, and special stains for micro-organisms were negative. Among the clinical presentations were folliculitis, vasculitis, acneiform eruptions, vesiculopustular lesions, and erythema nodosum-like lesions, with the legs, arms, and upper back being the most commonly involved sites. Nineteen patients were found to have specific underlying systemic diseases, namely, inflammatory bowel disease, Reiter's disease, Behcet's disease, hepatitis B, connective tissue disease including mixed connective tissue disease and rheumatoid arthritis, scrofuloderma, and hematologic dyscrasias. The other patient had antecedent bacterial sinusitis in the setting of atopy. The folliculocentric nature of these lesions may reflect preferential processing of antigens through the hair follicle and/or homology between bacterial and follicular heat shock proteins in the susceptible host, namely, one who responds excessively to exogenous antigenic triggers. Folliculitis with folliculocentric vasculopathy may be a clue to underlying systemic disease and/or an extracutaneous infection. Certain light microscopic features in concert with the clinical presentation may distinguish such cases from conventional infectious folliculitis.     

Churg‐Strauss syndrome presenting as scar reactivation: histopathologic features and an illustration of ‘locus minoris resistentiae’

We report a 33‐year‐old female with cutaneous involvement by Churg‐Strauss syndrome confined to surgical scars that were obtained 13 years before. She presented to the emergency department with 2‐day history of fever, night sweats, right‐sided weakness, hoarseness and worsening asthma symptoms. She was found to have an eosinophilia and two sub‐5‐mm pulmonary nodules. The patient also reported that the scars on her right thumb, inner wrist and back had been swollen, red and painful for 2 days. Examination revealed tender, erythematous, well‐healed edematous scars studded with small skin colored papules. She had no clinical findings that were classic for cutaneous vasculitis. A skin biopsy of a scar revealed perivascular and palisading granulomatous inflammation consisting of histiocytes and neutrophils with leukocytoclasia. Focal vascular injury was identified. Scattered tissue eosinophils were seen. Special stains were negative for infection. Thereafter, she was started on intravenous steroids, at which point the fever, pulmonary and cutaneous symptoms subsided. Although scar sarcoidosis is a well‐described phenomenon, granulomatous inflammation and vasculitis seen in Churg‐Strauss syndrome exclusively manifesting in well‐healed surgical scars highlights the unique features seen in this case and draws attention to the concept of locus minoris resistentiae. This case also highlights how a skin biopsy in the setting of suspected systemic vasculitis can confirm the presence of vasculitis and/or granulomatous inflammation and obviate the need for more invasive, higher risk procedures such as lung biopsy.     

Erythema Induratum with Pulmonary Tuberculosis: Report of Three Cases

Three cases of erythema induratum which occurred in the patients with pulmonary tuberculosis are described. The cutaneous lesions were violaceous, indurated nodules on both lower legs above the malleoli. Histologically, tuberculoid granuloma with caseation necrosis was found in one case; necrotizing vasculitis was the prominent finding in other two cases. The erythema induratum promptly responded to antituberculous therapy. We believe that, in light of these cases, the association between erythema induratum and infection with tubercle bacilli should be re-emphasized.     

Palisaded neutrophilic granulomatous dermatitis with leukocytoclastic vasculitis in a patient without any underlying systemic disease detected to date

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare dermatologic condition which shows various clinical and histopathological features. Although the PNGD lesions have been suggested to begin as leukocytoclastic vasculitis (LCV), there is still insufficient clinicopathological information in the reported cases of PNGD in acute stage with LCV. The relationship between PNGD and interstitial granumatous dermatis (IGD) also remains unclear. This report presents the case of a 60‐year‐old female patient with multiple erythematous nodules on the extremities. She had no underlying systemic disease detected to date, although transient, abnormal liver function tests were seen. The histopathological examination of an erythematous nodule revealed the features of PNGD in the acute stage. The patient presented the characteristic features of LCV including palisaded granulomatous pattern, and the interstitial granulomatous pattern was seen together, suggesting that PNGD with LCV can show an interstitial granulomatous pattern. The present case also suggested that PNGD in the acute stage with LCV tends to clinically manifest as erythematous nodules on the extremities and histopathologically shows a remarkable papillary edema and an extensive fibrin deposition in and around the vessel wall. PNGD may be associated with transient liver dysfunction. Misago N, Shinoda Y, Tago M, Narisawa Y. Palisaded neutrophilic granulomatous dermatitis with leukocytoclastic vasculitis in a patient without any underlying systemic disease detected to date.     

Sibutramine (Reductil?)-Induced Cutaneous Leukocytoclastic Vasculitis: A Case Report

A 24-year old woman presented with hemorrhagic vesicles on her legs. She had taken sibutramine (Reductil®, Abbott Labs., Seoul, South Korea) for 3 months and developed skin lesions the week before. A skin biopsy showed leukocytoclastic vasculitis with conspicuous eosinophilic infiltration of the tissue. These lesions showed improvement after discontinuation of sibutramine. However, 3 months later the skin lesions recurred on other sites on the lower extremities when the patient was rechallenged with the same drug for 2 weeks. Herein, we report the first case of necrotizing vasculitis induced by sibutramine.     

The spectrum of inflammatory skin disease following jejuno-ileal bypass for morbid obesity

From a scries of 105 patients who had undergone jejuno-ileal bypass for morbid obesity, seven developed an episodic illness featuring inflammatory skin lesions, usually associated with a non destructive polyarthritis. Tenosynovitis, myalgia and fever had also occurred. The illness abated spontaneously in four patients. The most characteristic skin lesion was an erythematous macule which developed a central vesicle or pustule. Erythema nodosum-like lesions and liquefying nodules were also seen. Early lesions were characterised by a dense accumulation of neutrophils. Changes in dermal vessels were less destructive than is usually seen in immune complex mediated vasculitis. Circulating immune complexes could be demonstrated in patients actively developing skin lesions. They were also found in some patients long after activity had ceased and in jejuno-ileal bypass subjects who had never developed inflammatory lesions. Dapsone was effective in suppressing the skin and joint symptoms when metronidazole and/or tetracycline had failed.