British loiinuilofDermatohgij {19^]) 124. 291-295.

ADONIS OOO7O963910OO68G

Adult lipophagic atrophic panniculitis

I.J.UMBERT AND R.K.WINKELMANN
Department of Di'miatolonn. Mttyo Clinic and Miuio i'oiinilatinti, Rochester. MJ\', U.S.A.
Accepted for publication 51 August 1990

Summary We report two patients with chronic, recurrent, nodular panniculiti.s lesions that later developed areas
of lipoatrophy. Histologicaily. there was a consistent lobular lipophagic replacement of fat cells with
lipophagic giant cells. The clinical appearance was that of tender, erythematous. superficial or
subcutaneous, symmetrical nodules and plaques of 1-2 weeks' duration. The lesions could occur with
episodes of fever. One patient had hepatomegaly and the other had an increased sedimentation rate
and ieucocytosis.
The histology and the clinical pattern of the panniculitus syndrome resembled those of lipophagic
lipoatrophy of childhood. This is a panniculitis of unknown cause in which the principal inflammatory
cell response in the subcutaneous tissue is the macrophage.

Descriptions of Weber-Christian panniculitis have Case reports

included the histology of lipophagic replacement of fat
Case 1
lobules since the early report by Weber.' Subsequently,
lipophagic replacement of fat has been used to define this A 47-year-oid womati was tirst seen in our department
syndrome as a pathological entity.- Pfeifer^ described a in February 1986. In November 1985 diffuse tender
2 3-year-old woman with primary lobular panniculitis. erythematous subcutaneous nodules and plaques had
lipoatrophy with lipophagia. and giant cells. The loca- developed on her right thigh and buttocks. No adeno-
tions of the lesions and muscle weakness were somewhat pathy and visceromegaly were found. Investigations
atypical and also raised the question of panniculitis with included a normal ultrasound of the pancreas and
connective tissue disease. normal serum amylase and lipase levels, negative anti-
I,ipophagia has recently been described as the primary nuclear antibody and normal levels of complement and
pathological process in a rare lipoatrophic syndrome of cryoglobulins. Cultures of the lesions for bacteria, myco-
panniculitis in childhood."^ All of these cases had been bacteria, and fungi were sterile. The level of Xi-antitryp-
called Weber-Christian disease or Kothman-Makai syn- sin was normal. Other investigations revealed that her
drome.'' '" Winkelmann ct ai'^ renamed these cases sedimentation rate was 8 mm/h (Westergren method)
lipophagic lipoatrophy of childhood, recognizing that and the haemoglobin level was 14 g/dl. Her leucocyte
the cases began with erythematous nodules of short count was 7-8 x 1()''/1, with a normal differential. Total
duration, with a recurrent course and lipophagic giant thyroxine. aspartate aminotransferase, cholesterol, and
cell replacement of fat. and with residual lipoatrophie triglyceride levels and blood chemistry values were
lesions. normal.
We have studied two adult patients with a similar The patient was started on dapsone, 50-100 mg daily
syndrome. All the features of the childhood phenome- and showed some resolution of her lesions. There were
non were present, and we wish to document this as a some broad atrophic depressions on the buttocks, thigh,
syndrome of panniculitis that can occur at any age. In and right arm at the sites of previous lesions (Figs 1 and
our experience this condition is unique in comparison to 21.
other forms of delineated panniculitis as in connective In March 1989 recurrent red nodules on both legs
tissue disease, pancreatic disease, or Xi-antitrypsin deti- developed, and 1 day later fever and chilis developed. She
ciency. was treated with dapsone and then sulphapyridine until
progressive weakness and shortness of breath developed.
Chest X-rays showed a diffuse bilateral inliltrate involv-
Correspondence: Professor K.K.WinkclniHnn, Depitrliiient of Dermato-
ing interstitial and alveolar components. These changes
logy, Mayo CWnk. 2(10 i'irst Street SW. Rocliestt-r. MN SS9()S. U.S.A. were consistent with a hypersensitivity pneumonitis.

291
292 I.|.LIMBERT AND R.K.WINKELMANN

Figure 1. (Case 1). Intiaminatory nodule on

anterior right thigh, April 19X9.

possibly due to sulphapyridine. The patient discontinued

the sulphiipyridine. with improvement of the clinical
signs and symptoms and clearing of the skin lesions. The
patient had no skin lesions 6 months later, except for the
previously developed lipoatrophy of the buttocks.

Case 2

A 57-year-old woman was first seen in onr department

in July 1980. Since January she had had very painful
indurated subcutaneous nodules and plaques over the
chest, back, abdomen, legs, arms, and breasts. These
occurred in crops, and the lesions lasted for 7-10 days.
She also had a temperature of up to 38' i°C and chills for
2-3 days, with generalized malaise accompanying the
eruption. On two occasions the lesions spontaneously
drained an oily material and resolved. Several lesions left
pigmented residual macules. Physical examination was
negative except for hepatomegaly. She had had an
intermittent arthritis of the right ankle with swelling and
tenderness and increased warmth since 1980.
Laboratory evaluation included negative tests with
purified protein derivative, a negative rheumatoid factor,
and normal blood cell counts except for occasions when
the leucocyte count was increased up to 17 x lO*^/!. She
had normal blood chemistry values. The blood sedimen-
tation rate varied from 30 to 120 mm/h. There were
normal throat and sputum cultures and samples of
Figure 2. (Caso 1). I.ipoa trophic lesions of buttocks in areas of previous sputum were negative for acid-fast bacilli and fungi. The
lipophaj^ic panniculitis, April 19S9. chest X-ray was normal. She also had normal antinuc-
 ADULT LIPOPHAGIC ATROPHIC PANNlCtJLITIS 293

Iear antibodies, normal C3, and normal blood cultures.

X-rays of the right ankle showed osteoporosis, and the
joint spaces were narrowed. Cultures of the tissue biopsy
specimens were negative for routine and anaerobic
organisms, mycobacteria. and fungi. She had normal
serum protein electrophoresis except for a mild elevation
of gamma globulin levels. Studies of the pancreas and
gastrointestinal tract were negative. The levels of 3:1-
antitrypsin. serum lipase. and amylase were normal on
three occasions. Urine amylase was normal. Creatine
phosphokinase muscle enzyme determinations were
normal.
She had been treated with diuretics and hydralazine in
the past 5 years for hypertension.
The patient was treated with systemic prednisone in a
dosage of up to 200 mg/day. Later, antimalarial drugs Figure 4. (Case 11. Mixture of lymphocytes and lipophages replacing
were added hut with no improvement of the clinical and surrounding tiit cells. Lipophage giant cells have characteristic
picture. Mild atrophy of the panniculns of the left calf central cluster of nuclei. IHaematoxylin and eosin: x27f).)
subsequently developed. Subsequently, the patient has
presented with several episodes of painful joint swellings
and multiple tender subcutaneous nodules associated also contained lymphocytes, a single large follicular-like
with cutaneous erythema and fever. germinal centre (Case 1). neutrophils. and plasma cells.
Numerous eosinophils were present in the infiltrate in
Case 1 and also were seen within the granuloma. There
hlistolotjii
was a superficial and deep perivascular infiltrate in the
The patients had lobular and septal lipophagic pannicu- dermis composed mostly of lymphocytes and histiocytes.
litis. The infiltrate was predominantly histiocytic, with a In Cases 1 and 2. the inflammatory infiltrate also
distinctive predominance of foamy histiocytes (lipo- surrounded the adnexal structures. The blood vessels
phages) and Touton-like lipophages that involved the were uninvolved. Focal fat necrosis was observed in Case
subcutaneous fat and periappendageal fat (Fig. 3). These 2. Two biopsy specimens of Case i irom 1986 and 1989
cells were confluent with a central mass of nuclei within showed an identical pathological picture with no sub-
the lipophagic giant cell cytoplasm (Fig. 4). The infiltrate stantial variation.
Macrocyst and microcyst formation were commonly
seen. Hxtensive fibrosis involving the subcutaneous
tissue was evident in Case 1. Special stains for bacteria,
fungi, and mycobacteria were negative. Polarization
microscopy failed to reveal any foreign material. Direct
; j^-^^.L^:^ •--^^r^-iiL^ y--: .-I ^^ immunofluorescence of involved skin in Case 1 showed
deposition of fibrinogen within vessels and IgM. IgA. and
C3-containing inflammatory cells in the fascia.
Monoclonal antibody studies of the tissue of Case 1
revealed 40% of cells positive for CD14 (Leu M3). a
monocyte antibody. Diffuse staining of small round cells
was present through the fat lobules, and 40% of the cells
•' •' . • ; • • • . • ' , - . ' . • V . n ^ , \ - - ^

• ^ W ' " ' # ^ ^ " ' - ^ • ' ^ • ' ^ - • . . ' . •••• ' • •-•••vi
were positive for CDS (Leu i) and CD 3 (Leu 4) pan-Tcell
markers. Some CD8 (Leu 2a) positive T-suppressor cells
were present in the lipophagic lobules. CD4 (Leu 5a)
positive T-helper cells were diffused through the infil-
trate, in a concentration of iO-4()%. Rare B cell nodules
1 i g u r i - S . K ' J I M ' I I. ( . ' n r i i p i r t f i i i h u h i r n p l ^ u i n i i ' i U h \ l i p i i p h a g o s i i l l d were identified hy CD22 (Leu 14). Staining for CD I
lipophagic giant cells. iHacmatoxyiiii and eosin: x 44.) (()KT6) was negative in the inflammatory fat but was
294 I.J.tJMBERT AND R.K.WINKELMANN

Tablr I. Ciist's ol'iiduit lipophagic lipoatrophy

Patient i^sion

Age Sex Location Duration Reference

2J F Face, breasts, arms Recurrent Pfeiler, 1892'

47 F Thigh 2 weeks Kooij, IS'SO'''
47 F Thigh, buttocks, tegs Recurrent [Imbcrt, Winkclmann, 1990
F Trunk, legs Recurrcnl

markedly positive for dendritic cells in the epidermis and Table 2. l.ipophagif panniculitis
hair follicles. CD38 (Leu 8) staining showed focal rare
isolated cells. Staining for CD7 (Leu 9) was negative. Primary
Acute, benign—children
Recurrent lipoatrophic—children
Discussion Acute or recurrent—Jidulls

We have found only one similar case of an adult patient Secondary

with multiple subcutaneous lipophagic panniculltis Erythema nodosum
nodules of the thigh lasting 2 weeks and leaving Erythemii induratum
lipomembranous panniculitis
lipoatrophy.''' The histopathology of this case was Mesenteric panniculitis
massive lipophage and giant cell lobular panniculitis. Fat necrosis of the breast
This case is included with our two cases of lipophagic Foreign body reaction
and lipoatrophic panniculitis of the adult (Table 1). This l re-excision
is an extremely rare syndrome in adults and could be
confused with other diseases.
Weber' described a patient witb tuberculosis and a
classical erytbema nodosum syndrome. Tbe histopatbo- cbiidhood and compared these cases with 14 similar
logy was similar to our present cases of lipopbagic cases from tbe literature. Four additional cases have
lobular panniculitis with lipophagic giant cells. His case subsequently been described by Larbre et n/.'" In tbese
is one of tbe index cases included in the collective cases tbere was a consistent replacement of fat lobules by
description of 'Weber-Cbristian disease'. The cliildbood lipopbagic histiocytes and lipopbagic giant cells. The
cases of Cummins and Lever^ also showed lipophagic disease was commonly recurrent, and erythematous or
panniculitis with lipoatropby. and were published as deep nodular lesions of panniculitis could be present.
Weber-Christian disease, as were additional paediatrlc Fever was frequently present. The lesions would last for
cases. It has been pointed out that cases of erythema 5 weeks or more. On occasions, large plaque lesions
nodosum may show lipophagia'*^-" which is also part of would coalesce, persist, and extend to cover extensive
otber disease states of tbe fat. areas. Five patients had evidence of liver disease as
In 1915. Galloway-' described large lipophages in a indicated by hepatomegaly, changes in the liver
patient witb erythema induratum. Several cases of enzymes, or on liver biopsy. One of our two current adult
erythema nodosum described as Weber-Christian dis- patients bad hepatomegaly.
ease demonstrated lipophages with some giant cells as The evolution of tbe lipoatrophy in the children gave
common findings.^- Lipopbages have also been found in rise to the 'hewn extremity sign". Tbis is similar to the
foreign body reactions.-' lipomembranous panniculi- large cupuliform atrophy seen in our adult patients with
tis.-^ mesenteric panniculitis.-'' fat necrosis of tbe this same histology.
breast.^''-' and re-excision of surgical specimens-'' A lipophagic panniculitis of benign course and rapid
(Table 2). self healing lesions has been described by Royer ct u/..-''
Recently. Winkelmann ('( ai^ described three patients Turpin and IJocquet.^'and Labeillei'l al " Tbis pannicu-
with an atropbic lipogranulomatous lipoatrophy of litis presents in cbildren witb or without fever or
 ADULT LIPOPHAGIC ATROPHIC PANNICULITIS 295

respiratory tract infection. These lesions beal sponta- .S Larkin V de P, De Sanctis AC Margulis Aii. Relapsing febrile
neously in 7-21 days and no treatment is necessary. The nodular nonsuppurative panniculitis (Weber-Christian disease):
review of the literature, with report of a case. Am j Dis Child 1944;
histopatbology Is of panlobular lipopbagic panniculitis
67: 120-5,
witb lipopbagic giant cells, Tbere is no lipoatrophy or 9 Fournier A. Pauli A. Panniculite nodulaire de Weber-Christ Ian
other residual of tbe lesions. chez une enfant dc deux atis. Pediatrie ] 9fi 5: 20: 59 5-600,
We conclude from tbese reports that tbe pathology of 1 i) Temime P. Mancy R, Maestraggi P ('(td. l.ipogranulomatose sous-
cutaneede Rothmann-Makai cbv7. une tillette. HullSor Fr Dermalol
lipopbagia can be primary or secondary. In primary
Sni'hllinr 19fi8: 75: 2()fi-7.
lipopbagia. no prior disease or injury to tbe subcuta- ] 1 I ndeutsch VV, Berger HF, l.ipogranulomatosis Rothmann-
neous tissue can be identified, and the syndromes listed Makai—eigenstiindiges Krankheitsbild oder polyatiologisches
in Table 2 as primary are idiopathic panniculitis with Syndrom? HiiiiUtrzi 1971); 21: 221-5.
lipophagia. The secondary responses include responses 12 Stanoeva L, Miovski D. Systemic form of Weber-Christian disease
with hepatic enlargement, Denmitoloiiiai 1972; 145: 48-55.
to known injury or inflammation. Some of these primary I i Allen-Mersh TC. Weber-Christian piinniculitis and auto-immune
reactions may be immunological, and some may be disease: a case report. / CIm PaUwl I97(i; 29: 144-9,
physical or toxic. It seems probable that the typical 14 Nowinska-U'bioda H, Dynowska U. l-ipogranulomatosis subcuta-
response occurs from some monokine stimulus released nea, Panniculitis Rothmann-Makai. Objaw 'obciosanych' kon-
czyn, I'rzi'nl l)i-rnuilol 1977; 64: 479-82.
from the inflammation or produced by some special host
I 5 Taylor GA. Prolonged remission of Weber Christian syndrome in
factor developing from tbe diffuse macrophage/lipo- an infant, Cliii tWimr {Phihil I9H1; 20: 521 J.
phage panniculitis. The monokine may originate from Id Fxjge |, Dunger UB, Dillon M), Weber-Cbristian panniculilis and
tbe T cells identified in Case 1. chronic active hepatitis. F.ur J Pediutr 1986: 145: 227-9,
] 7 Moragon M, Jorda B, Ramon .MD ft al. Atrophie connective tissue
The patients described in tbis paper represent an panniculitis, Inl / nenmiwl 1988; 27: 18 5-6.
extremely rare variation of primary lipopbagia that 1 H Larbre F, Larbre H, DeParscauL. U'spanniculitesouadiponecroses
developed lipoatrophy. The bistopatbology is character- multinodulaires primitives de I'enfant. Pfdunru- I 989; 44: 19 5-6,
19 Kooij R. Weber Christian's disease, a form of spontaneous panni-
istic. The response to treatment is variable, but cortico-
culitis. DmrnUoloi/Jni 1950; 1(11: 5 52-44,
steroids used early can prevent much of tbe lipoatrophy 21) Winkelmann RK, Torstrom I,. New observations in the histopatho-
and the inflammatory signs and symptoms. It seems to logy of erythema nodosum. / Invest Dermatoi 1975: 65: 441-6,
us tbat tbis is equivalent to the disease as observed in 21 tialloway |, Case of erytbema induratum giving no evidence of
cbildren. and on tbat basis, we suggest that in tbese tuberculosis, lir I l)ermatol 191 J: 25: 217-25.
22 Panush RS, Yonkcr RA, DIesk A et iil. Weber-Christian disease:
patients a complete investigation of liver function sbould analysis of 15 cases and review of the literature. Xieiiicine
be performed. Oiidtimim-i 1985:64: 181-91.
2 3 Kellner H. Zur I'rage der Zusammenhiinge zwischen lipophager
Granulombildung und Erythema induratum, Sarcoid Darier-
Roussy und Panniculilis nonsuppuraliva nodularis rezidivans,
References Hautarzt 1951:2:299-305,
1 Wchcr FP. A case of relapsiny, non-suppurtitive nodular panniculi- 24 Alegre VA. Winkelmann RK, Aliaga A. Lipomembranous changes
tis, showing phagocytosis of subcutaneons fat-cells by macro- in chronic pannicutitis, / Am Aaid Dcrmatol 1988; 19: 39-46,
phagcs. Br I DiTimwl 1925: 37: M ) l - l l , 25 Wexner SD. Attiyeh FF, Mesenleric pannicuiitis of the sigmoid
2 I^ver WK, Schaumhurji-Lever G, Histopalhohgii of the Skin. 7th colon; report of two cases. Dis Ciilon Retliim 1987; JO; H 1 2-5.
edn, Philadelphia: |B Lippincott Company, 1990: 27S-7, 26 Oppermann A, Philippe !•:. WehtT B, C.ranulome lipopbagique
i Pl'eifer V, I'eber einen Kail von herdweiser Atrophie des suhcuta- premammaire bilateral, Ann Amit Puthol (('(iris) 1964; 9: 179-8 J,
nen IVttgewcbes. Dlsch Anh Fr Klin Med 1S92: ^0: 4JK-49. 27 KeynesC^ A case of fat necrosis of the breast, lir I Stirneui 192 5:12:
4 Winkclmann RK, McEvoy MT, Peters MS, Upophagic panniculilis 66 5-5,
of childhood, / Am Aaid Derimitol I9S9; 21: 971-S. 28 Zelickson RD, Winkelmann RK. Lipophagic panniculitis in reexci-
5 ttilchrist TC. Ketron 1.W, A unique case ofatrophy of the fatty layer sion specimens, Aclii Denn Venereol \Stockh) |in press),
of the skin, preceded by the ingestion of the fal by large phagocytic 29 Royer P, Schweisguth 0, Habib R, L-adiponecrose multinodulaire
eells—macrophages. Johns Hopkins Hosp Hull ]9l(i: 27: 291-4, disseminee aiguc non recidivante de I'enfanl. Si'm Hop Paris I 958;
6 Cunitniiis L|. li-ver WF. Relapsinj; febrile nodular nonsuppurative J4: 1 5 H - 7 .
panniculitis (VVeber-Chrislian disease): report of two cases. Arch }() Turpin R, Bocquet L, Panniculite aigue benigne. Scin Hop Paris
Dernuitol Sfiplulol I9J8: I8:4]5-2f>. 1959: JS: 1793-6,
7 Pinetti P. l.a malattia di Cristian-Weber: pannicolite nodulare non SI Laheiile 13, FraitagS, ,Mardyla Ec( al. Adiponecrose multinodulaire
suppurutiva recidivante e lebbrile. G lial Dernmloi Sifilol 1941; 82: disseminee aigui" non recidivante de I'enfant, Ann Oermalol
297-J4(). Venereo! 1988; 115: 1] 34-5.