Subcutaneous Granuloma Annulare Research Articles

Subcutaneous granuloma annulare of the eyelid: A case report

A rare case of subcutaneous granuloma annulare of the eyelid is reported. A diabetic patient developed a unilateral periorbital tumorous mass. Biopsy revealed subcutaneous palisading granuloma. By microscopy and immunohistology, other granulomatous reactions including necrobiosis lipoidica could be ruled out. Since treatment with dapsone was without effect, the tumor was surgically excised. The differential diagnosis and the literature are briefly discussed.

Pseudorheumatoid Nodule (Deep Granuloma Annulare) of Childhood: Clinicopathologic Features of Twenty Patients

Pseudorheumatoid nodule of childhood is seen uncommonly by pathologists and is thought to be a variant of granuloma annulare. We report a series of 20 patients (13 M, 7 F) age 1 to 17 years. Fourteen lesions arose on the front of the lower limb, and 14 children had numerous lesions at diagnosis. Seven developed some form of recurrence, except for one case occurring at the site of the original lesion. Only one patient had a weakly positive rheumatoid factor, and was the patient with remote recurrence. As a significant number of lesions arose around the foot when the child was beginning to walk or starting to wear shoes, it is suggested that trauma plays a role in the development of some of these lesions.

Subcutaneous Granuloma Annulare

Subcutaneous granuloma annulare (SGA) is a benign inflammatory disorder that occurs in children. The profiles of 12 children with SGA who were diagnosed and treated at our institution were reviewed. The patients presented with a rapidly growing, painless soft-tissue mass of the extremities or scalp. Parental concerns of malignancy and lack of recognition of this condition by the physician led to excessive diagnostic testing and, on occasion, inappropriate therapy. The mean age at presentation was 3.9 years, and the mean follow-up after biopsy study was 3.4 years. The lesions were most commonly located about the elbow, knee, and scalp. While complete blood count, erythrocyte sedimentation rate, and plain radiographs were helpful in ruling out other conditions, no ancillary test was specific for this disorder. In all cases, definitive diagnosis required a biopsy sample. Excisional biopsy was diagnostic but not therapeutic, because 75% of the children had one or more recurrences of this condition at either local or distant sites. Two of the subsequent lesions resolved spontaneously, and no child within the study group has progressed to any recognized systemic illness or connective-tissue disorder.

Rheumatoid Nodule and Subcutaneous Granuloma Annulare

We performed histologic and selected histochemical and immunohistochemical studies on rheumatoid nodules (RN) from 12 patients and lesions of subcutaneous granuloma annulare (SGA) from nine patients. The mean age for patients with RN was 56 years, while that for SGA patients was 19 years. In contrast to those with RN, none of the patients with SGA had arthritis. RN tended to show homogeneous, eosinophilic necrobiosis, giant cells within palisaded foci, and significant stromal fibrosis; while lesions of SGA showed pale, edematous necrobiosis, an absence of giant cells, and lesser degrees of fibrosis. The single most helpful histochemical method was alcian blue, which stained necrobiotic foci in all cases of SGA but in only one case of RN. Epithelioid cells in both disorders stained positively for muramidase. IgM was found in vessel walls in two cases of RN. While the mechanisms of these disorders are not entirely clear, it appears that RN can usually be reliably distinguished from SGA on histologic grounds alone.

Granuloma annulare: A rare occipital lesion in infants and children

Subcutaneous granuloma annulare is a rare scalp lesion that occurs in infants and children. Occurrence in the occipital region, absence of bone involvement, slow growth, and foci of necrosis of collagen surrounded by palisading granulomatous inflammation are characteristic of this lesion. Although the cause remains unknown, it is not infectious and is more likely due to a defect in cell-mediated immunity. The prognosis after excision is excellent. Increased awareness that this peculiar granulomatous lesion can rarely occur in the soft tissue of the occipital region will help prevent confusion with neoplastic or infectious processes.

Subcutaneous palisading granulomas (benign rheumatoid nodules) in children

Subcutaneous palisading granulomas (SPG), also known as benign rheumatoid nodules, occur in otherwise healthy children. Although these lesions have the same histology as rheumatoid nodules in adults, subcutaneous granuloma annulare, and diabetic lipoidicum, they appear to represent a distinct clinicopathologic entity. We reviewed our experience with 17 cases of SPG. All patients presented with one or more painless, nonmobile, subcutaneous nodules. Lower extremity involvement was most common, but lesions presented in the upper extremities and scalp as well. There were 14 girls and three boys ranging in age from 10 months to 15 2 12 years (mean, 4 5 12 years) at the time of diagnosis. Past medical histories were negative. Laboratory and radiologic studies were normal except for one child with an elevated erythrocyte sedimentation rate (ESR). The follow-up period ranged from 6 months to 14 10 12 years (mean, 4 11 12 years). Subsequent new lesions developed in nearly two thirds of the patients. In the one child with an initially elevated ESR, rheumatoid arthritis developed. All others were alive and well except for one who died in a motor vehicle accident without evidence of further disease. Preoperative diagnosis was correct in only three patients. Excisional biopsy was performed in all cases. However, one child had reveived prior radiation therapy, one received topical steroid therapy, and three patients had subsequent lesions excised. All subsequent lesions not surgically excised underwent spontaneous involution. Our findings together with a review of 160 cases in the literature led us to conclude that (1) SPG should be considered in the differential diagnosis of painless, subcutaneous masses in children, (2) laboratory tests on children with SPG should include an ESR, and (3) other than a diagnostic biopsy of the initial lesion further treatment is usually not indicated.

Epithelioid sarcoma and isolated necrobiotic granuloma: a comparative immunocytochemical study

Epithelioid sarcoma (ES) occasionally may be confused, both clinically and histologically, with isolated necrobiotic granulomas (ING), leading to misdiagnosis and potential mismanagement of these conditions. We studied 11 cases of ES and 11 of ING (6 examples of deep granuloma annulare and 5 of rheumatoid nodule) immunohistochemically, in an attempt to determine whether they could be diagnostically separated by such means. Monoclonal antibodies to cytokeratin polypeptides (CK), epithelial membrane antigen (EMA), and leukocyte common antigen (LCA) were applied to formalin-fixed, paraffin-embedded sections in each case, using the avidin-biotin-peroxidase complex technique. All ES cases stained positively for CK, and 6 expressed EMA, while examples of ING were non-reactive for these antigens. Conversely, the large epithelioid histiocytic cells in cases of ING were immunoreactive with anti-LCA, whereas no case of ES displayed this determinant in tumor cells. In the latter lesions, reactive peritumoral inflammatory cells were LCA-positive, but were readily distinguished from neoplastic cells on morphological grounds, as well as by their negativity with anti-CK and anti-EMA. Based on these data, it is concluded that immunohistologic stains for epithelial and hematopoietic antigens are valuable in the conclusive diagnostic separation of epithelioid sarcoma and necrobiotic granulomas.

Intracellular elastin in generalized granuloma annulare

This report reviews thirteen cases of generalized granuloma annulare. The light and electron microscopic appearance of intracellular elastin particles in eleven of these cases is described. These bodies were also noted in deep granuloma annulare, elastosis perforans serpiginosa, and a small percentage of localized granuloma annulare. They were not found in necrobiosis lipoidica.

Subcutaneous granuloma annulare of the finger

Granuloma annulare is a cutaneous disorder, which may be associated with subcutaneous fibrosis. Subcutaneous granuloma annulare lesions may occur without the cutaneous manifestations, and often biopsy is required for diagnosis. We report subcutaneous granuloma annulare of the index finger without cutaneous manifestations, in a 19-year-old woman. Diagnosis was confirmed by excision and histologic examination. In the natural history of granuloma annulare, a spontaneous resolution can be expected. No other specific treatment is necessary.

Eosinophils in the cellular infiltrate of granuloma annulare.

Eosinophils have been described in the infiltrates of granuloma annulare, but their frequency, distribution and extent are not well documented. We found eosinophils in 18/45 (40%) cases of granuloma annulare, without significant variation relating to histologic sub-pattern. Eosinophils were seen in over half the cases of deep granuloma annulare and in over one-third of the cases of superficial granuloma annulare. This study demonstrates the lack of specificity of eosinophils in differentiating superficial granuloma annulare from deep granuloma annulare, granuloma annulare from necrobiosis lipoidica, and granuloma annulare from occasional clinical simulants which histologically show eosinophils, such as arthropod bite reactions.

Pseudorheumatoid Subcutaneous Nodules and the Poststreptococcal State

A 10-year-old girl with an acute illness fulfilling the Jones criteria for rheumatic fever is described. She had subcutaneous nodules, arthritis, an elevated ESR, and serologic evidence of a recent streptococcal infection. Her clinical course was benign and at ten weeks, the nodules disappeared, the joint pains had subsided, and the ESR was normal. Thus, there was little to support a diagnosis of rheumatic fever. We hypothesize that the patient had pseudorheumatoid subcutaneous nodules coincidental with poststreptococcal arthritis. A revision of the Jones criteria disallowing subcutaneous nodules as an independent major sign of rheumatic fever is proposed.

The subcutaneous nodule: Its significance in the diagnosis of rheumatic disease

Summary A wide variety of cutaneous and subcutaneous nodules are seen clinically. By far the most common of these is the rheumatoid granuloma, occurring at pressure points in patients with rheumatoid arthritis. These nodules are often of long duration and generally imply severe disease. In contrast, the now uncommon rheumatic nodule is transient and does not manifest the typical trizonal architecture of central necrosis, palisading histiocytes, and surrounding fibrosis, so typical of the rheumatoid nodules. The rheumatic nodule does not correlate with severity of arthritis in rheumatic fever but is strongly associated with cardiac involvement. The rheumatoid variant arthritides are not associated with nodules, although rare patients with nodules have been reported. Patients with systemic lupus erythematosus and Jaccoud arthritis may develop typical rheumatoid nodules. It is claimed that the nodules of juvenile rheumatoid arthritis more closely resemble the rheumatic nodule than the rheumatoid nodule. Numerous reports of children without arthritis describe subcutaneous nodules with histology identical to the rheumatoid nodule. These are known as pseudorheumatoid nodules. They do not precede the onset of arthritis and are probably part of the spectrum of granuloma annulare. Necrobiosis lipoidica diabeticorum likewise shares a very similar histology with the rheumatoid nodule. The subcutaneous adiposa is the site of numerous inflammatory nodules that can be grouped together under panniculitis. In erythema nodosum, nodular panniculitis (Weber-Christian disease), lupus profundus, and the nonsystemic cutaneous vasculitides, angiitis plays a prominent role in the pathogenesis. Pancreatic disease in which direct enzymatic cytolysis occurs is an exception to this rule. The skin manifestations of the systemic angiitides are diverse, and nodules are among the least common of the dermal manifestations, with the exception of the frequent eruptions in Behcet disease. Gout, amyloidosis, and hypercholesterolemia represent metabolic disorders in which normal body materials accumulate in excess, with resultant nodular deposition in cutaneous tissue and in or around joints (tendons). The tophus can closely mimic the rheumatoid nodule clinically. Likewise, the nodules and arthropathy of amyloidosis have been confused with rheumatoid disease. Only two storage diseases, multicentric reticulohistiocytosis and Farber disease, cause both subcutaneous nodules and arthritis. The bacterial pathogens producing nodules and arthritis include the treponemal organisms, syphilis, yaws, and pinta, as well as leprosy. Erythema nodosum leprosum is probably an immune complex-mediated reaction. Among the fungi, coccidioidomycosis is a well-described cause of erythema nodosum and arthritis. Disseminated sporotricosis rarely produces juxtaarticular nodules and arthritis. Of the viruses associated with arthritis only the hepatitis B virus has been documented to produce both arthritis and subcutaneous nodules. This uncommon association may also represent an immune complex-mediated phenomenon. Finally, such miscellaneous conditions as osteoarthritis and Dupuytren contracture are common causes of nodular disease which can be clinically confusing to the uninitiated.

Subcutaneous Granuloma Annulare ("Pseudorheumatoid Nodule") of the Eyebrow

Subcutaneous granuloma annulare occurs either as a single or multiple lesion. When the ocular adnexa are involved, the lateral aspect of the eyelid and the lateral canthus are sites of predilection. These lesions occur chiefly in children and only rarely in adults. They have the same clinical (and histopathological) appearance as rheumatoid nodules and are, therefore, also known as "pseudorheumatoid nodules." Despite this similarity, these nodules are isolated lesions and are not related to systemic disease, including rheumatoid arthritis and rheumatic fever. The presently reported case exemplifies the characteristic clinical and pathological features of this disorder.

Pseudorheumatoid Nodules of the Ocular Adnexa

A clinicopathologic study of 21 cases revealed pseudorheumatoid subcutaneous nodules occurring in the eyelids and periorbital region of children and young adults. These nodules were most frequently located in the lateral upper eyelids and outer canthal region, and in five cases they were multiple. The lesions recurred in about 20% of the cases. In addition, new lesions located elsewhere were observed in 26% of cases. Histopathologically they resembled the subcutaneous nodules of rheumatoid arthritis and rheumatic fever. Follow-up information on 15 patients (from two to 12 years) and the results of laboratory studies on seven patients had failed to reveal any association with these two systemic diseases. Pseudorheumatoid nodules may be indicated when a healthy child or a young adult presents with solitary or multiple subcutaneous nodules, especially in the eyelids. These lesions pursued a benign clinical course and local excision, which is usually performed for diagnostic purposes, was the only treatment indicated. The lesions had a tendency to regress spontaneously; therefore, local recurrences should be treated conservatively by periodic follow-up examinations.

Pseudoxanthomatous Rheumatoid Nodules

Two cases of patients with an unusual form of rheumatoid nodules closely resembling tendon xanthomas are reported. The disease process was mistakenly diagnosed by numerous physicians as xanthomatosis in one case and as gouty tophi in the second case. The differential diagnosis of rheumatoid nodules rests on clinical and laboratory findings plus histologic confirmation. Occasionally, the onset of nodule formation antedates the onset of arthritis, adding to diagnostic confusion. This is to be distinguished from the entity, pseudorheumatoid nodules, which has been proposed to explain those rare cases where clinically and pathologically typical nodules persist over many years without the development of associated signs of rheumatoid arthritis. The development of x-ray demonstrable "punched out" bony radiolucencies in association with subcutaneous rheumatoid nodules is stressed.

Subcutaneous Granuloma Annulare

Five cases are reported as examples of the subcutaneous form of granuloma annulare. Classical cutaneous lesions appeared at approximately the same time in cases 1 and 2; in other instances (cases 3 and 4) the subcutaneous lesions preceded the classical ones; a brother of this last patient (case 4) presented only subcutaneous nodular lesions (case 5). Although biopsy was not performed, his eruption was regarded as an example of subcutaneous granuloma annulare because of the morphologic features, course, spontaneous regression, and the sibling association. Because of the paucity of reported examples of familial incidence of granuloma annulare a description of a cousin of the two siblings (cases 4 and 5) who presented classic cutaneous (but not subcutaneous) granuloma annulare has been included (case 6). These related children had their disease concurrently.