A granuloma annulare-like eruption associated with the use of amlodipine

A granuloma annulare-like drug reaction is a rarely encountered clinical entity. A 64-year-old Caucasian female developed a granuloma annulare-like reaction 13 days after starting amlodipine and cleared within 3 months after drug cessation. The eruption consisted of multiple erythematous pruritic papules, distributed symmetrically over the lateral aspects of the legs and thighs, as well as on both palms. Histology showed focal collagen degeneration and significant interstitial histiocytic dermal infiltrate suggestive of granuloma annulare. We review previously reported cases of granuloma annulare-like drug reactions, in the context of a recently proposed classification for drug-induced interstitial granulomatous reactions.     

Delayed reaction after an octopus bite showing a giant cell-rich granulomatous dermatitis/panniculitis

Adequate clinical data and a sufficient workup, in addition to the histopathological findings, are frequently required to make a correct diagnosis of granulomatous dermatitis/panniculitis. These lesions with an unexpected etiology may include delayed hypersensitivity granulomatous reactions to various factors, such as metals or marine animal injuries. A 50-year-old male presented with multiple subcutaneous nodules on his right forearm 1 month following an octopus bite at his right wrist. After the disappearance of these lesions, which responded well to low-dose oral prednisone, another type of skin lesion characterized by small, numerous papules reappeared on his right forearm. Histopathologically, a specimen from a subcutaneous nodule showed mostly lobular granulomatous panniculitis, which showed an extensive diffuse infiltrate composed of numerous multinucleated giant cells and epithelioid cells intermingling with lymphocytes and eosinophils. A specimen from a papule that subsequently developed disclosed a diffuse granulomatous dermatitis composed of similar cells and also showed granuloma annulare-like features. This case is considered to be a delayed reaction after an octopus bite showing an unusual giant cell-rich granulomatous dermatitis/panniculitis. Octopus bites should therefore be included among the marine animal injuries, which cause a delayed-type reaction with granulomatous dermatitis/panniculitis.     

淋巴瘤伴发皮肤肉芽肿的现象及其意义

淋巴瘤可伴发皮肤肉芽肿,其模式主要有两种:一种是淋巴瘤的特异性皮损中出现肉芽肿反应,例如肉芽肿性蕈样肉芽肿和肉芽肿性皮肤松弛症;另一种是淋巴瘤出现非特异的肉芽肿性皮损,主要见于一些系统性淋巴瘤.其组织病理学类型可为结节病样、环状肉芽肿样、结核样等.其机制及其与预后的关系尚不明确.肉芽肿形成可能是造成某些淋巴瘤特殊临床表现的原因,也容易掩盖淋巴瘤的真实面目,在临床和组织学诊断上需谨慎.     

Interstitial granulomatous lesions as part of the spectrum of presenting cutaneous signs in pediatric sarcoidosis

Abstract:  Skin findings in childhood sarcoidosis vary greatly, but only a few occurrences have been published in which the histopathology has been characterized well. We describe a child with sarcoidosis in whom the cutaneous findings were atypical, resembling granuloma annulare. Histologic examination of these cutaneous lesions, however, revealed areas of sarcoid-like epithelioid cell granulomas, a palisading granulomatous process with features of granuloma annulare, as well as palisading neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis. This underscores the variability of skin findings in childhood sarcoidosis—even within the same patient—and suggests that sarcoidosis should be considered in the differential diagnosis of children initially diagnosed with granulomatous skin lesions, such as granuloma annulare, palisading neutrophilic, and granulomatous dermatitis or interstitial granulomatous dermatitis, who demonstrate associated signs of systemic disease.     

Peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement: a clinicopathologic study of four cases

Epithelioid granuloma formation has rarely been observed in specific cutaneous lesions from T-cell lymphomas other than those of mycosis fungoides/Sézary syndrome (MF/SS). Three patients diagnosed with nodal and/or extranodal (tonsillar) non-Hodgkin's peripheral T-cell lymphoma (PTCL) and one patient with angioimmunoblastic T-cell lymphoma (AILD), developed specific cutaneous involvement showing prominent epithelioid cell and/or granulomatous inflammation. The original diagnostic lesions had no granulomatous features. In addition to a specific lymphomatous infiltrate, prominent dermal and/or subcutaneous granulomatous infiltrates were observed. Sarcoid-like granulomas were observed in two patients (one of them presented a granuloma annulare-like pattern in early lesions), granulomatous panniculitis was noted in one patient and in one patient with AILD, masses of epithelioid cells were noted. The clinicopathological features of cutaneous involvement by PTCL showing a florid epithelioid and/or granulomatous cell reaction are reviewed. Various histopathological patterns can be observed. The diagnostic difficulties of these cases are stressed.     

Facial granulomatous diseases: a study of four cases tested for the presence of Mycobacterium tuberculosis DNA using nested polymerase chain reaction

The histopathologic diagnosis of cutaneous tuberculosis (CTB) is often troublesome, because there are several other entities (tuberculids, demodicidosis, granulomatous rosacea, and acne agminata) that may display granulomatous inflammation with caseation necrosis. The current study describes four cases of granulomatous disease of the face. The final diagnosis (assessed on the basis of the clinical response to therapy) was CTB in three cases and granulomatous rosacea in one case. Histologically, epithelioid granulomas were a constant feature; in one case of CTB, they displayed a palisading (granuloma annulare-like) arrangement. Caseation necrosis was a prominent feature only in the case of granulomatous rosacea. Routinely processed biopsy specimens were evaluated with nested polymerase chain reaction (nPCR) for Mycobacterium tuberculosis (MBT) DNA. The correlation between nPCR results and clinical outcome was less than optimal; in fact, one case showed an excellent clinical response to the antituberculous drug therapy despite the absence of MBT DNA amplification. In granulomatous diseases of the face, the importance of evaluating not only nPCR but the overall clinicopathologic picture so as to avoid diagnostic misinterpretations is emphasized.     

Granuloma annulare-like infiltrates with concomitant cutaneous involvement by B-cell non-Hodgkin's lymphoma: report of a case

Granulomatous infiltrates, including granuloma annulare-like changes, in patients with T-cell non-Hodgkin's lymphoma and Hodgkin's disease are well described but are exceedingly uncommon in B-cell non-Hodgkin's lymphoma. Herein, we describe a 73-year-old male with a 10-year history of B-cell chronic lymphocytic leukemia who developed erythematous annular plaques symmetrically on his upper extremities. Biopsies of these lesions revealed both granuloma annulare-like areas, in conjunction with nodular atypical lymphoid infiltrates consistent with secondary involvement by B-cell chronic lymphocytic leukemia. To our knowledge, this is the first report of cutaneous lesions resembling granuloma annulare with concomitant involvement by B-cell chronic lymphocytic leukemia. Awareness of this association may prevent nonrecognition of a neoplastic B-cell infiltrate in a granuloma annulare-like process.     

Granulomatous periorificial dermatitis

Granulomatous periorificial dermatitis (GPD) is a distinct facial eruption in prepubertal children that should be distinguished from granulomatous rosacea, perioral dermatitis, and cutaneous sarcoidosis. We describe a case of GPD and review the key distinguishing features of this condition.     

Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis

Palisaded neutrophilic granulomatous dermatitis (PNGD) is an entity that has not been clearly defined either clinically or histopathologically. It is seen in patients with rheumatoid arthritis and other connective tissue diseases. In the past, many cases of PNGD have been described under several different names including palisaded neutrophilic and granulomatous dermatitis, linear subcutaneous bands, interstitial granulomatous dermatitis with cutaneous cords and arthritis, rheumatoid papules, and Churg-Strauss granuloma. We report 7 additional cases of PNGD. Clinically, 6 patients presented with erythematous to violaceous plaques, papules, and nodules on multiple body sites; one presented with subcutaneous linear bands on the shoulder. Five had rheumatoid arthritis; one had adult-onset Still's disease; and one showed clinical signs of rheumatoid arthritis, although serologically the rheumatoid factor was negative. On histologic examination, a spectrum of changes was observed ranging from urticaria-like infiltrates to leukocytoclastic vasculitis and granuloma annulare with neutrophils. We report these cases to expand the histologic spectrum of this entity and to further delineate the different forms of clinical presentation.     

Non-Infectious Granulomatous Diseases of the Skin and their Associated Systemic Diseases

Non-infectious granulomatous diseases of the skin are a broad group of distinct reactive inflammatory conditions that share important similarities. As a group, they are relatively difficult to diagnose and distinguish both clinically as well as histologically. Many of these disorders have significant associations with systemic diseases that impact the patient’s overall prognosis. In this update, we offer a discussion of emerging concepts and controversies in this field, as presented through evidence-based answers to seven important clinical questions regarding palisading and epithelioid granulomata. These questions offer an opportunity to review ten non-infectious granulomatous conditions that have implications for systemic disease: granuloma annulare, annular elastolytic giant cell granuloma, necrobiosis lipoidica, methotrexate-induced accelerated rheumatoid nodulosis, necrobiotic xanthogranuloma, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, palisaded neutrophilic granulomatous dermatitis, sarcoidosis, and metastatic Crohn disease. Recent clinical, epidemiologic, and laboratory studies have shed some light on these diseases, the association of these conditions with systemic disorders, and their overall prognoses.     

Churg‐Strauss syndrome with coexistence of eosinophilic vasculitis,granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid‐like blisters

The main histopathological features in the cutaneous lesions of Churg‐Strauss syndrome (CSS) are dermal leukocytoclastic vasculitis with a variable eosinophilic infiltrate and non‐vasculitic tissue eosinophilia with granuloma formation. This wide histopathological spectrum may account for the various skin manifestations of CSS. However, the unique histopathological combination of dermal eosinophilic vasculitis and subcutaneous granulomatous phlebitis accompanied by bulla formation has not been previously described. We report an unusual CSS case showing dermal necrotizing eosinophilic vasculitis and granulomatous phlebitis in purpuric lesions coupled with subepidermal blistering. The blisters showed dermal granulomatous dermatitis and eosinophilia without evidence of vasculitis. Dermal necrotizing eosinophilic vasculitis was characterized by fibrinoid alteration of the vessel wall, a prominent perivascular eosinophilic infiltrate, a few infiltrating histiocytes along the affected vessel wall, and the absence of neutrophilic infiltration. The underlying subcutaneous granulomatous phlebitis was characterized by an angiocentric histiocytic infiltrate surrounded by marked eosinophilic infiltrate. Deposition of cytotoxic proteins and radicals derived from eosinophils in the vessel walls and papillary dermis followed by a secondary granulomatous response may account for the unique clinical and histopathological features in this case. Ishibashi M, Kudo S, Yamamoto K, Shimai N, Chen K‐R. Churg‐Strauss syndrome with coexistence of eosinophilic vasculitis, granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid‐like blisters.     

Herpes zoster granulomatous dermatitis: histopathologic findings in a case series

Several types of cutaneous reactions have been reported to arise at the site of herpes zoster (HZ) infection weeks to years after the acute disease. Among these, granulomatous reactions are the most frequently reported. In this study, we describe the spectrum of histopathologic findings of HZ granulomatous reactions observed in 26 patients with cutaneous lesions confined to the area of previous HZ eruption and compare them with biopsy specimens taken from 25 patients with acute HZ. All patients with persistent reactions from whom history was available presented within 12 weeks of the onset of the acute eruption. The most frequent findings were interstitial granulomatous dermatitis with lymphocytes, histiocytes and multinucleated giant cells displaying elastophagocytosis and a perineural, perivascular and perieccrine mononuclear inflammatory infiltrate rich in lymphocytes and plasma cells. Less common features included intra‐arrector and peri‐arrector pili granulomas, follicular dilatation and hyperkeratosis, and vasculitis. Specimens from patients with acute HZ were found to have small numbers of perineural plasma cells and most had subtle granulomatous inflammation, in patterns similar to the group with late granulomatous reactions. Our findings suggest that granulomatous reactions to varicella zoster virus represent a persistent evolving inflammatory reaction after acute infection.     

Mycobacterium marinum infection simulating interstitial granuloma annulare: a report of two cases

We report two cases of Mycobacterium marinum infection that histologically simulated interstitial granuloma annulare (GA). In one case, an infectious etiology was not suspected in histologic sections, but a tissue culture performed during the patient's clinic visit identified M. marinum, and a subsequent Fite stain revealed mycobacteria. Interstitial granulomatous dermatitis is a rare presentation for cutaneous nontuberculous mycobacteria and has yet to be attributed specifically to M. marinum. In both immunocompetent and immunosuppressed patients, infection with M. marinum should be considered in lesions histologically resembling interstitial GA, particularly when there is clinical suspicion for an infectious process.     

Granulomatous mycosis fungoides with small intestinal involvement and a fatal outcome

We report a case of granulomatous mycosis fungoides that progressed into fatal gastrointestinal involvement 4 years after the onset of skin lesions, despite improvement of the skin lesions in response to a combination of PUVA and systemic interferon-gamma therapy. Histological examination showed Pautrier's microabscesses with granuloma annulare-like features and sarcoidal granuloma formation in the plaque stage, proliferation of blast-transformed atypical lymphocytes with persistent granuloma formation in the tumour stage, and metastatic lesions. A literature review of granulomatous mycosis fungoides revealed that 11 of the 24 reported cases died of the disease, and like our case, seven died within 5 years. We suggest that mycosis fungoides with granulomatous reactions does not indicate a favourable prognosis.     

The frequency of dual TCR-PCR clonality in granulomatous disorders

Background: A granulomatous infiltrate in association with cutaneous T‐cell lymphoma is uncommon. The diagnosis of mycosis fungoides can be difficult in the setting of an exuberant granulomatous infiltrate that obscures the neoplastic lymphoid infiltrate, thereby mimicking a granulomatous dermatitis. Therefore, the clinical context and supplemental molecular analysis, such as the demonstration of a monoclonal T‐cell population, may assist in diagnosis. Monoclonal T‐cell populations have been reported in association with inflammatory conditions and serve as a diagnostic pitfall. The frequency of T‐cell clonality in association with granulomatous dermatitides has not yet been established. Methods: We identified 29 patients with granulomatous dermatitis who had biopsies at two distinct body sites. Results were correlated with clinical follow up and with clonal T‐cell receptor‐gamma chain rearrangement as detected by polymerase chain reaction‐based analysis (dual TCR‐PCR). Results: Clinical follow up was obtained in 17 of 29 cases (58.6%). Twenty‐five of 29 cases of granulomatous dermatitis lacked T‐cell monoclonality. Three cases of granuloma annulare contained a T‐cell clone in one of the two biopsies. One case of necrobiotic xanthogranuloma showed an identical T‐cell clone in multiple biopsies. Conclusions: The use of dual TCR‐PCR analysis, that is, T‐cell clonality analysis in biopsy specimens from two different sites, serves as an adjunct to assist in distinguishing granulomatous inflammatory reactions from granulomatous T‐cell lymphoma, including granulomatous mycosis fungoides. The occasional finding of a T‐cell clone in a granulomatous dermatitis underscores the importance of clinicopathological correlation in daily diagnosis. Dabiri S, Morales A, Ma L, Sundram U, Kim YH, Arber DA, Kim J. The frequency of dual TCR‐PCR clonality in granulomatous disorders.     

Cutaneous reactions at sites of herpes zoster scars: an expanded spectrum

Several types of cutaneous lesions have previously been described at the sites of herpes zoster scars. We describe 16 patients with cutaneous lesions which had developed on herpes zoster scars. Biopsies were taken from these lesions, and a polymerase chain reaction assay was used to detect the viral genome in paraffin-embedded specimens. Histopathological findings enabled diagnosis of nonspecific granulomatous dermatitis in five patients, granulomatous vasculitis in two patients, lichen sclerosus in two patients, and pseudolymphoma, keloid, sarcoidal granuloma, granuloma annulare, granulomatous folliculitis, lichen planus and cutaneous Rosai–Dorfman disease, each in one patient. Varicella-zoster virus DNA was not identified in any of the patients. Granulomatous folliculitis, lichen sclerosus and cutaneous Rosai–Dorfman disease have not previously been described in herpes zoster scars, but they are three new cutaneous reaction patterns that may have developed within these scars. Our investigations indicate that the cutaneous reactions appearing in herpes zoster scars are not due to the persistence of varicella-zoster virus DNA within the lesions.     

Interstitial granulomatous dermatitis with plaques

BACKGROUND: Interstitial granulomatous dermatitis is a histopathologic pattern with variable clinical appearance associated with autoimmune systemic diseases. The frequency of its different cutaneous expressions and its association with autoimmune diseases are not known. OBJECTIVE: We describe the clinical, serologic, and histologic features in 17 patients with interstitial granulomatous dermatitis with a clinical presentation consisting of large erythematous plaques. METHOD: Skin biopsy specimens fulfilling criteria for diagnosis of interstitial granulomatous dermatitis were selected and correlated with the clinical and laboratory findings. RESULTS: The study included 1 man and 16 women with multiple, asymptomatic, round to oval, erythematous plaques, most often on folds of the skin, in a bilateral and somewhat symmetric distribution. Most of patients had rheumatoid polyarthralgias along with various serologic abnormalities, often connected to collagen vascular diseases. Histologic examination disclosed a distinctive interstitial granulomatous dermatitis characterized by a diffuse infiltration of the interstitium by histiocytes with piecemeal fragmentation of collagen and formation of small granulomas around degenerative areas in concert with variable numbers of polymorphonuclear leukocytes sprinkled within the infiltrate. Churg-Strauss granulomas in miniature and flame figures were occasionally observed and indicated continued or increased activity of the associated autoimmune disease(s). CONCLUSIONS: Interstitial granulomatous dermatitis with plaques is a distinct entity with highly reproducible clinical and histopathologic features; recognition of these features identifies a patient who may have an underlying systemic autoimmune disorder.     

Cutaneous sarcoidosis and primary biliary cirrhosis: A chance association or related diseases?

Sarcoidosis and primary biliary cirrhosis (PBC) are thought to be two distinct disorders of unknown origin. However, both are characterized by hepatic granuloma formation and may also manifest cutaneous granulomatous inflammation. In this report, we describe two cases of cutaneous sarcoidosis occurring in the setting of PBC and review 7 additional cases from the literature of granulomatous skin disease associated with PBC. Although the pathogenesis of both sarcoidosis and PBC remains elusive, the simultaneous occurrence of these uncommon diseases suggests a common pathway may contribute to granuloma formation in both disorders.     

Interstitial granulomatous dermatitis with plaques.

We report on the clinical and histopathologic findings of four patients who had asymptomatic, erythematous to violaceous plaques symmetrically distributed on the upper aspect of the thighs, lateral chest, and in two cases also on the abdomen and flexor surface of the elbows. All of the patients were women; two of them had arthritis, which in one case was associated with an autoimmune disorder, and another had autoimmune thyroiditis. Histopathologically, all cases showed similar changes consisting of an interstitial granulomatous dermatitis involving mostly the lower reticular dermis. Histiocytes were the predominant cellular component, arranged interstitially and in small palisades around foci of degenerated collagen bundles in concert with large numbers of neutrophils and eosinophils. Interstitial granulomatous dermatitis can present different clinical expressions, including linear cords, papules, and, as in our cases, plaques. This peculiar histopathologic pattern falls into the spectrum of cutaneous extravascular necrotizing granuloma, a condition that is often associated with systemic autoimmune disease.     

An unusual presentation of secondary syphilis in a patient with human immunodeficiency virus infection. A case report and review of the literature.

BACKGROUND--Syphilis has been reported to assume unusual clinical appearances and to exhibit unusual courses in patients infected with the human immunodeficiency virus (HIV) type 1. We recently observed a distinct manifestation of syphilis in an HIV-infected patient with features not previously described. OBSERVATIONS--A 38-year-old HIV-seropositive homosexual man presented with fever, chills, malaise, and a cutaneous eruption consisting of indurated, shiny, erythematous plaques that were confluent on the face and scalp leading to alopecia and extreme tautness of the skin. Initial clinical diagnoses included lymphoreticular malignancy and infection. Although cultures yielded Staphylococcus aureus, a skin biopsy specimen was diagnostic of syphilis. CONCLUSIONS--This case demonstrates an unusual clinical manifestation of syphilis in a patient with HIV infection and emphasizes the importance of considering cutaneous secondary syphilis in the differential diagnosis of virtually any inflammatory cutaneous disorder in HIV-seropositive individuals.