Lipoatrophic Panniculitis Case Report and Review of the Literature

OBSERVATION Lipoatrophic Panniculitis Case Report and Review of the Literature

Lisa Y. Shen, BS; M. Bruce Edmonson, MD, MPH; Gary P. Williams, MD; Chethana Chandrupatla Gottam, MD; Molly A. Hinshaw, MD; Joyce M. Teng, MD, PhD

Background: Lipoatrophic panniculitis (LP) is a rare added later to the regimen as a steroid-sparing agent, and disease of childhood characterized by eruption of ten- the dose was increased over the course of 3 months, by der erythematous nodules and plaques followed by cir- which time the cutaneous disease progression was nearly cumferential bands of lipoatrophy often seen on the arms halted. However, the patient continued to have lower leg and legs. This condition has also been known as lipo- pain with bone changes demonstrated on magnetic reso- phagic panniculitis of childhood, annular atrophy of the nance imaging. ankles, and partial lipodystrophy. Conclusions: We report this case and review of the lit- Observations: A previously healthy 8-year-old boy was erature to call attention to the clinical features of LP and evaluated for tender, raised plaques on the ankles, which its association with skeletal changes. Our patient’s re- progressed to circumferential atrophy of the distal lower sponse to combination therapy is of interest and con- extremities. Biopsy specimen analysis revealed a dense tributes to the limited literature about management of mixed infiltrate extending into the subcutaneous tissue this disease. as well as lipophages within the fatty lobules. A diagnosis of LP was made, and the patient began treatment with prednisone and hydroxychloroquine. Methotrexate was Arch Dermatol. 2010;146(8):877-881

IPOATROPHY REFERS TO THE REPORT OF CASE loss of subcutaneous fat and may be classified as gener- A previously healthy 8-year-old boy de- alized, partial, or localized.1 veloped tender, raised plaques on the lat- Lipoatrophic panniculitis eral aspects of his ankles and had been (LP)L is a form of localized lipoatrophy that given the diagnosis of granuloma annu- typically presents on the extremities with lare initially. Over the course of 6 months, tender erythematous nodules and plaques the lesions progressed circumferentially that enlarge radially and leave residual cir- around the ankles and spread to the calves cumferential bands of lipoatrophy. Clini- with edema, thickening, tenderness of the cally, it may resemble many conditions, in- skin, and increased atrophy and inflam- cluding granuloma annulare, morphea, mation (Figure 1). He remained afe- erythema nodosum, foreign body granu- brile during the 6 months, complaining of lomatous reaction, deep erythema annu- moderate pain, especially near the advanc- lare centrifugum, tumid lupus, erythema ing borders. The findings from a com- migrans, cellulitis, and urticarial vasculi- plete review of systems were otherwise tis. However, it can be differentiated from negative. His family history was signifi- other disorders via characteristic histo- cant for Crohn disease. There was no ad- logic features of lipophagic panniculitis enopathy noted on examination, and the and absence of vasculitis.2 Reported treat- patient had normal range of motion. ments include prednisone, antimalarial Two biopsy specimens were obtained Author Affiliations: agents, saturated solution of potassium io- from the right medial calf and dorsal as- Departments of Pediatrics dide, dapsone, and azathioprine, each with pect of the right foot. Histopathologic (Drs Edmonson, Williams, and different efficacy profiles.2-13 We report Teng) and Dermatology analysis revealed a dense inflammatory in- (Drs Gottam, Hinshaw, and herein a case of an 8-year-old boy with pro- filtrate composed primarily of large his- Teng), University of Wisconsin gressive LP who responded well to a com- tiocytes, multinucleated giant cells, and School of Medicine and Public bination of prednisone, hydroxychloro- small collections of neutrophils infiltrat- Health (Ms Shen), Madison. quine, and methotrexate. ing the lower reticular dermis and extend-

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Figure 1. Circumferential bands of lipoatrophy seen in lipoatrophic panniculitis. A, Left foot and ankle. B, Right lower leg.

A B

Figure 2. Biopsy specimens obtained from the right medial calf (hematoxylin-eosin). A, Dense inflammatory infiltrate composed primarily of large histiocytes, multinucleated giant cells, and small collections of neutrophils infiltrating the lower reticular dermis and extending into the subcutaneous fat (original magnification ϫ40). B, Lipophage within fatty lobule (upper left) (original magnification ϫ400).

ing into the subcutaneous fat (Figure 2). No vasculitis neutrophil cytoplasmic antibody, peripheral antineutro- or polarizable foreign body was identified. Numerous li- phil cytoplasmic antibody, anti–Saccharomyces cerevi- pophages were evident in the fatty lobules. Periodic acid– siae antibody, antinuclear antibody, alpha 1-antitrypsin Schiff, Gomori methenamine silver, acid-fast bacilli, and phenotype, primary immunodeficiency, Lyme disease, and Warthin-Starry stainings revealed no microorganisms. human immunodeficiency virus (HIV) antibody. Given the patient’s family history of Crohn disease, a Nine months into the course of his symptoms, the pa- workup consisting of abdominal and pelvic computed to- tient was referred to our institution, where it was noted that mography, upper and lower endoscopy, and biopsies were the disease process had skipped to other areas of his body, performed, and all findings were within normal limits. including new involvement of both wrists and the left but- Laboratory results were also within normal limits, with tock and left posterior thigh. These new lesions were ac- the exceptions of a repeatedly elevated erythrocyte sedi- companied by pain, tenderness, and redness. The patient mentation rate (ESR) (up to 51 mm/h), mild normo- had a weight of 25.4 kg, height of 128.3 cm, and body mass cytic anemia, and an elevated platelet count (592ϫ103/ index of 15.4 (calculated as weight in kilograms divided uL). (To convert platelets to numberϫ109/L, multiply by height in meters squared), which represents approxi- by 1.0.) Assay results were also normal for quantitative mately the 50th percentile for each characteristic. Find- immunoglobulins (IgA, IgG, and IgM), circulating anti- ings from the rest of his skin examination were within nor-

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C D

Figure 3. Clinical arrest of panniculitis after 3 months of therapy. A-D, There remains circumferential lipoatrophy of ankles and lower calves as well as isolated areas of lipoatrophy on the posterior left thigh and left buttock.

mal limits. There were no clinical signs of insulin resistance, of LP was made. The patient began treatment with pred- such as acanthosis nigricans. He underwent further labo- nisone (20 mg/d, approximately 1 mg/kg) and hydroxy- ratory evaluations, including complete blood cell counts, chloroquine (100 mg/d) and showed a rapid initial re- a complete metabolic panel, and assays of pancreatic en- sponse of decreased edema and erythema. However, his zymes, thyroid function, tissue transglutaminase anti- disease relapsed when the prednisone dose was tapered body, anti-microsomal antibody, C-reactive protein, and to 10 mg/d, resulting in increased tenderness and ery- ESR. All laboratory test results were within normal limits thema. Ten months into the illness, methotrexate was except the ESR, which was elevated to 30 mm/h. added to the treatment regimen as a steroid-sparing agent, Based on the clinical features and classic histologic find- given as 15-mg intramuscular weekly injections, then ing of lipophages within the fatty lobules, the diagnosis gradually increased to 25 mg weekly over the course of

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Cases, Source No./Sex/Age, y Affected Areas Associated Diagnoses Treatment; Outcome Winkelmann et al2 12/F and 5/M Legs (n = 14), feet NR Observation (n = 6); remission in 1 of 6 (n = 17) Age range, (n = 2), thighs Prednisone (n = 8); remission in 8 of 8 Ͻ1to11a (n = 10), arms Chloroquine (n = 1); remission in 1 of 1 (n = 9), trunk (n = 5), Prednisone and chloroquine (n = 2); remission face (n = 4) in0of2 Martinez et al7 1/F/3 Arms, legs, buttocks Chromosome 10q26 Prednisolone and azathioprine; good response (n=1) abnormality (complication, avascular necrosis of bilateral femoral heads) Billings et al5 1/M/3 Arms, legs Rheumatoid arthritis Prednisone; complete response (n=3) 1/F/6 Arms, legs Type 1 DM, Hashimoto Potassium iodide solution; no response thyroiditis 1/M/9 Legs Type 1 DM First episode, no treatment; spontaneous resolution Second episode, prednisone; complete resolution Roth et al3 1/F/4 Ankles, thighs, knees NR Combined prednisone and dapsone; halted (n=1) disease progression 4 Madasseri et al 1/F/41⁄2 Ankles, calves NR Combined prednisone and dapsone; halted (n=1) disease progression Dimson and Esterly6 1/F/6 Ankles, calves Graves disease, Observation; atrophy remained localized and (n=1) alopecia areata stable Shelley and Izumi8 1/F/6 Ankles NR Corticosteroid cream under occlusion and cold (n=1) quartz light; skin appeared normal, and atrophic bands remained unchanged Falcini et al10 1/F/8 Legs NR Prednisone; complete response (n=1) Melchiorre et al9 1/F/12 Calves NR Prednisone and pentoxifylline for 3 mo; good (n=1) response Handfield-Jones et al13 1/F/24 Cheeks, upper outer Raynaud phenomenon Hydroxychloroquine (400 mg/d) and (n=2) arms, buttocks, prednisolone (30 mg/d); suppressed active thighs lesions, but lesions reappeared on tapering of prednisolone dose to Ͻ20 mg/d 1/F/32 Face, trunk, proximal NR Dapsone, azathioprine, and antimalarial agents; extremities unsuccessful Corticosteroids; effective (complication, avascular necrosis of femoral head) Hydroxychloroquine; remission Nelson12 1/F/36 Ankles, calves NR Observation; no new lesions after 2 y (n=1) Umbert and Winkelmann11 1/F/47 Buttocks, thigh, arm NR First episode, dapsone; complete resolution (n=2) Second episode, sulphapyridine added to dapsone regimen; not tolerated 1/F/57 Trunk, legs, arms, NR Prednisone (up to 200 mg/d) combined with breasts antimalarial drug; no response

Abbreviations: DM, diabetes mellitus; NR, not reported. a Age reported as range only for entire study population; youngest patient was aged 0.67 years.

3 months. The prednisone dose was gradually tapered COMMENT over the course of the next 6 months. His ESR decreased to 2 mm/h, with clinical cessation of the progression of his panniculitis but with focal areas of atro- Progressive LP is also known as lipophagic panniculitis phy remaining (Figure 3). of childhood, annular atrophy of the ankles, and partial Despite the improvement of his skin lesions, the pa- lipodystrophy. It has a distinctive clinical presentation tient continued to have pain localized to his lower legs. and histologic findings but usually lacks systemic find- Magnetic resonance imaging of the calves revealed in- ings. Clinically, there are eruptions of erythematous nod- creased T2-weighted signal from the subcortical and cor- ules and plaques followed by a striking circumferential tical bone within the mid shaft of both tibiae, most con- band of lipoatrophy, principally of the arms and legs. As- sistent with a stress reaction. However, no definite fracture sociated laboratory findings include elevated ESR, throm- was identified. A bone mineral density measurement bocytosis, and microcytic anemia.2 The end-stage atro- showed normal status for chronologic age. At last follow- phic phase of disease is chronic, but this condition is up, the patient had cessation of lipoatrophy maintained otherwise self-limited and not fatal. Differential diag- for 12 months and continued to respond well to metho- noses include “noninflammatory” lipoatrophy and in- trexate therapy. flammatory lipoatrophy or lipodystrophy. Dunnigan-

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©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 type familial partial lipodystrophy type 2 and juvenile larial agents, saturated solution of potassium iodide, and dermatomyositis are examples of conditions mimicking dapsone, all of which have varying degrees of efficacy. Our LP in addition to the inflammatory conditions listed patient responded well to a combination of prednisone, hy- herein. Lipoatrophic panniculitis is distinct from these droxychloroquine, and methotrexate. We present our case entities in that there are no other systemic disease pro- to contribute to the growing body of literature on this rela- cesses present. Histologically, a characteristic feature of tively uncommon entity and to call attention to potential lobular panniculitis with histiocyte and lipophage re- associated skeletal problems. Further studies are needed placement of the fat is seen. There is notable absence of to determine the efficacy of various treatment options for vasculitis or phlebitis. this progressive disease. Very few pediatric cases of LP have been docu- mented to date (Table).2-10 Although the cause is un- Accepted for Publication: January 6, 2010. known, an association with autoimmune conditions has Correspondence: Joyce M. Teng, MD, PhD, Depart- been proposed. Billings et al5 have described 3 patients ment of Dermatology, University of Wisconsin School of with LP in addition to autoimmune diseases such as dia- Medicine and Public Health, 1 S Park St, Seventh Floor, betes mellitus type 1, Hashimoto thyroiditis, and juve- Madison, WI 53715 ([email protected]). nile rheumatoid arthritis. Dimson and Esterly6 also re- Author Contributions: All authors had full access to all ported the case of a 6-year-old girl with a history of Graves of the data in the study and take responsibility for the disease and alopecia areata who subsequently devel- integrity of the data and the accuracy of the case report. oped annular lipoatrophy of the ankles. It has also been Study concept and design: Edmonson, Williams, and Teng. proposed that a genetic link may exist, as evidenced by Acquisition of data: Edmonson, Williams, and Hinshaw. a chromosome 10q26 abnormality in a 3-year-old girl with Analysis and interpretation of data: Shen, Edmonson, Got- a 12-month history of rapidly progressing acquired li- tam, and Teng. Drafting of the manuscript: Shen, Got- poatrophy.7 tam, Hinshaw, and Teng. Critical revision of the manu- Lipoatrophic panniculitis may also have associated joint script for important intellectual content: Shen, Edmonson, and skeletal findings. Shelley and Izumi8 first reported Williams, Gottam, and Teng. Administrative, technical, radiographic changes in a 6-year-old girl with annular and material support: Shen, Edmonson, Williams, Got- atrophy of the ankles: radiography revealed increased tam, and Teng. Study supervision: Shen, Edmonson, growth lines in the underlying tibiae (representing bone Gottam, and Teng. regrowth after temporary cessation of longitudinal growth) Financial Disclosure: None reported. but no bone cysts. Melchiorre et al9 reported the case of a 12-year-old girl with lipophagic panniculitis with pain- REFERENCES ful bilateral ankle synovitis and erythema along the pe- roneal tendons. Radiography did not reveal any bony ab- 1. Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. 2nd ed. London, England: Mosby; normalities, but magnetic resonance imaging showed 2007. extensive edema of the distal lower extremities, includ- 2. Winkelmann RK, McEvoy MT, Peters MS. 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