- Email: [email protected]
Delayed and persistent cutaneous reactions to coelenterates
I I
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I
IIIII
i
Ill
Delayed and persistent cutaneous reactions to coelenterates Kenneth M. Reed, M . D . , Ben R. Bronstein, M.D., and Howard P. Baden, M.D.
Boston, MA Three patients are described who developed firm, persistent papules and plaques at sites of previous contact with two species of coelenterates. Histologically, a predominantly mononuclear inflammatory cell infiltrate located primarily in the reticular dermis was observed with destruction of hair follicle epithelium and arrectores pilorum. Epidermal changes included focal spongiosis and exocytosis of lymphocytes. The eruptions subsided no sooner than 7 weeks from time of onset. It is hypothesized that this cutaneous reaction represents a persistent delayed hypersensitivity response to an antigenic component of the coelenterate nematocyst. (J AM ACADDERMATOL 10:462-466, 1984.)
Cutaneous reactions to marine organisms are common but have received little attention in the dermatologic literature. The pathophysiology of the immediate sting reaction has been carefully elaborated with respect to certain marine organisms, t'' However, little information exists concerning the histopathologic events that develop subsequent to the initial sting. Although an acute necrotic response consistent with a sting reaction is most commonly observed initially following contact with coelenterates, a a nonspecific superficial type of acute dermatitis has also been described. 4 Chronic cutaneous reactions to coelenterates have not been well studied. Following Echinoidea (sea urchins) contact, however, a sarcoid-like or foreign b o d y - l i k e granulomatous response has been described after latent periods of up to 12 months s-7 This report describes the hisFrom the Departments of Dermatology and Patllology (Dermatopathology Unit), Harvard Medical School, Massachusetts General Hospital. Accepted for publication Juls' t l , 1983. Reprint requests to: Dr. Howard P. Baden, Department of Dermatology Warren 5, Massachusetts General Hospital, 32 Fruit St., Boston, MA 02114/617-726-3993.
462
topathologic changes in three patients who developed a delayed and persistent cutaneous reaction after contact with coelenterates. CASE REPORTS Case 1 A 28-year-old woman was stung by a jellyfish on her right knee, arm, and cheek while swimming off the Greek island of Mykonos during the month of September. The sites rapidly became erythematous and pruritic but cleared spontaneously within 3 days. After 1 week, erythematous, edematous plaques with a vesicular component developed at sites of previous contact and were treated with a corticosteroid cream (Fig. 1). This therapy did not result in any improvement, and she was placed on a course of prednisone with an initial dose of 60 mg daily that was tapered over 2 weeks and resulted in clearing. However, the lesions recurred several days after stopping the drug. Biopsy of a cheek lesion during the recmTence (2 months after the sting) revealed slight focal hyperkeratosis and diffuse mild spongiosis (Fig. 2). Slight basal layer vacuolization was evident focally. The edematous papillary dermis contained occasional lymphocytes and melanin-laden macrophages, primarily in a perivascular distribution. Within the reticular dermis, a massive infiltrate of small and large lymphocytes and
Volume 10 Number 3 March, 1984
Cutaneous reactions to coelenterates
. ",
463
~ ! ,~i-..i.::~". ) ~ r :;"':4"'r~" " "'.. ". . ~.~j
N Fig. 1. Case 1. A well-demarcated red plaque is seen on
[
the right cheek. occasional histiocytes surrounded numerous dermal vessels and infiltrated between individual collagen bundles (Fig. 2). Interspersed among the small and large lymphocytes were focal nodular collections of large lymphoid cells with cleaved and noncleaved nuclei and some epithelioid-like cells with abundant cytoplasm. These collections resembled germinal centers; however, where epithelioid-like cells were aggregated, early granuloma formation could not be completely excluded (Fig. 2). The lymphohistioeytic infilttzte invaded several hair follicles that demonstrated spongiosis of the outer root sheath epithelium (Fig. 3). No foreign material was noted with the use of incident and polarized light microscopy. The eruption recurred after a second course of prednisone and finally subsided spontaneously 5 months after the initial contact.
Case 2 A 26-year-old woman contacted a file coral while swimming in the Virgin Islands and developed an immediate stinging sensation at points of contact. An erythematous and pruritic papular eruption developed 4 days later on her left leg and ankle. The eruption resolved spontaneously 7 weeks after the time of contact. Biopsy of a papule from the leg obtained 1 month after the sting occurred revealed focal parakeratosis and spongiosis with exocytosis of small lymphocytes. Within the edematous dermis, there was a superficial and deep primarily perivenular lymphohistiocytic infiltrate containing numerous eosinophils. No foreign material was identified with the use of incident and polarized light microscopy.
Fig. 2. Case 1. There is a dense, diffuse lymphohistiocytic infiltrate present primarily within the reticular dermis; focal aggregations of large lymphocytes and epithelioid-like cells are present (arrowheads). Slight spongiosis and exocytosis of Iymphocytes are seen in the overlying epidermis and follicular epithelium (F). (Hematoxylin-eosin stain; original magnification, • 160.)
Case 3 A 29-year-old woman contacted what she thought was a fire coral while snorkeling in the Virgin Islands. Within minutes she developed hivelike lesions that cleared rapidly coincident after taking diphenhydramine. During the next 7 days, a linear arrangement of firm erythematous papules and plaques developed at the sites of contact. The eruption faded spontaneously 2 months after the initial episode. Biopsy of a papule from the leg performed 6 weeks after the contact showed slight, diffuse epidermal spongiosis, with focal exocytosis of small lymphocytes and focal basal layer vacuolization. In the papillary dermis, prominent edema and a perivascular lymphohistiocytic infiltrate were observed. The infiltrate extended to the deeper portions of the dermis disposed about vessels and surrounded and invaded hair tbllicles, eccrine glands, and, most prominently, arrectores pilorum. The latter appeared markedly disrupted by this infiltrate (Fig. 4). No foreign material was identified with the use of incident and polarized microscopy. COMMENT These cases represent cutaneous reactions to members of the phylum Coelenterata, which are delayed in onset and persistent. Of the 9,000 or so
464
Reed et al
r ~ ~,.~.
I
Journal of the American Academy of Dermatology
~""
"~-. ,,
~'~'
.
.
~
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,
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~ t~
Fig. 3. Case 1. Within two hair follicles (F) are prominent lymphocytic infiltration and spongiosis. The infiltrating ceils are primarily small lymphocytes. (Hematoxylin-eosin stain; original magnification, x 400.)
species of coelenterates, only about seventy have been implicated in injuries to man or are known to be capable of penetrating human skin. 8 This phylum has been subdivided into three classes. The first, Hydrozoa, includes hydroids, Portuguese man-of-war, and the fire coral (Cases 2 and 3). Scyphozoa comprise the second class of coelenterates and the category to which jellyfish (Case 1) belong. The third class, the Anthozoa, includes sea anemones and true corals? All coelenterates have in common a structure, composed of a capsule and tube, known as the nematocyst. In the capsule is a coiled thread that, when uncoiled and ejected, pierces the skin and discharges its toxic contents through its long filamentous tube? This uncoiling can be triggered by either chemical or mechanical stimuli. Nematocysts are distributed widely in the epidermis of coelenterates and are present in large numbers on the tentacles of these organisms. Once the nematocyst has penetrated the skin, toxins that may be released include quarternary ammonium compounds, proteins, 5-hydroxytryptamine, catecholamines, histamine, and histamine liberators. ~''~ These substances produce the erythema and edema seen in acute sting reactions and contribute to the sensations o f pain and pruritus. However, little is known
Fig. 4. Case 3. This arrector pili has been infiltrated and partially destroyed by the dense mononuclear inflammatory cell infiltrate. (Hematoxylin-eosin stain; original magnification, x 400.) about the incidence of persistent cutaneous reactions to coelenterate stings or about their pathogenesis. In speculating about underlying cellular mechanisms, we recognized that the histologic appearance of the biopsy specimens from our three patients bore certain resemblances to previous histologic studies of delayed hypersensitivity reactions in humans. Black et al I~ examined delayed hypersensitivity reactions occurring after intradermal injection of purified protein derivative of tuberculin and noted primarily a perivascular lymphocytic infiltrate with focal intervenular extension. In a more detailed study Dvorak et al, 12 with the use of sections 1 /~m thick, demonstrated prominent perivascular infiltrates composed primarily oflymphocytes, with some macrophages extending into the deep dermis and subcutis. The infiltrates were less pronounced in the intervascular areas of the dermis. Basophils were observed in approximately 60% of cases, while eosinophils were observed in only two of the thirty-six cases. Using paraffin-embedded hematoxylin and eo-
Volume 10 Number 3 March, 1984
sin- stained sections, we observed a lymphohistiocytic infiltrate centered primarily around dermal venules in Patients 2 and 3. However, in Patient 1, the dermal inflammatory cell infiltrate permeated the intervascular dermis as well. Patient 1 further differed from delayed hypersensitivity reactions by demonstrating prominent infiltration of hair follicles and arrectores pilorum and this was also true for Patient 3. Eosinophils were prominent in the infiltrate only in Patient 2. Basophils cannot be evaluated in routinely processed biopsy specimens. Within the intervenular infiltrates in Patient 1, there were focal aggregates of large mononuclear cells vaguely resembling germinal centers, a finding not observed in the studies of Dvorak et al. t"- Interestingly enough, "pseudolymphoma" has been reported in association with prolonged reactions to insect bites and allergy hyposensitization injections.~3,~4 As in most of the cases reported by Dvorak et al, epidermal changes, including focal spongiosis and infiltration of the epidermis by !ymphocytes, were noted in all three biopsies. These changes may be secondary to the underlying dermal inflammation and edema. Furthermore, in two of the three cases focal hyperkeratosis or parakeratosis was evident, findings which may be related to the chronicity of these lesions. If we hypothesize that the observed tissue reactions are related to a prolonged delayed hypersensitivity (cell-mediated immune) response to intradermally injected antigen, the histologic differences observed between our study and the studies of Black et al 1~and Dvorak et al ~z may be related to the persistent nature of the immunologic response. The reactions in the present cases were documented as late as 2 months after presumed intradermal (and/or subcutaneous) antigen injection. Similarly, cutaneous reactions up to 2 years in duration to arthropod bites have been reported. ~3 The histologic appearances of such lesions differ from those in this study by the presence of a large number of eosinophils, some plasma cells, and prominent epidermal hyperplasia.t3 No nematocysts or other foreign material could be identified in the tissue sections examined by reduced illumination, by polarized light, or with
Cutaneous reactions to coelenterates
465
the reticulin stain. The latter has been found useful in identifying nematocysts, which are impregnated with silver? Foreign body or sarcoid-like granulomatous reactions reported to result from injury by sea urchins, ~'~ were not observed, although some loci in Patient 1 suggested early granuloma formation. The presence and exact nature of the antigen(s) responsible for eliciting the observed inflammatory responses cannot be determined in tissue sections by currently available technics. Therefore, direct evidence for the role of coelenterate antigen(s) in provoking the reactions in these three cases is speculative. A similar mechanism has been suggested by Meneghini* for the delayed component of sea urchin dermatitis. In that study, Meneghini was able to produce a dermal delayed hypersensitivity reaction with the use of intraderreal injection of water-alcohol extracts of sea urchin spines in two fishermen with sea urchin granulomas.* *Meneghini CI: Cases of sea urchin granulomawith positive intradermal test to spine extracts. Contact Dermatitis Newsletter 12:316, 1972. REFERENCES 1. Hashimoto Y: Marine toxins and other bioactive marine metabolites. Tokyo, 1979, Japan Scientific Societies Press. 2. Halstead BW: Poisonous and venomous marine animals of the world. Princeton, NJ, 1978, Darwin Press. 3. Kingston CW, Southcott RV: Skin histopathology in fatal jellyfish stinging. Trans R Soc Trop Med Hyg 54:373-384, 1960. 4. DeOreo GA: Dermatitis venenata resulting from contact with marine animals (hydroids). Arch Derrnatol Syph 54:637-649, 1946. 5. Fisher AA: Dermatitis caused by echi.noderms, in Atlas of aquatic dermatology. New York, 1978, Grune & Stratton Inc., pp. 27-34. 6. Rocha G, Fraga S: Sea urchin granuloma of the skin. Arch Dermatol 85:406-408, 1962. 7. Kinmont PDC: Sea urchin sarcoidal granuloma. Br J Dermatol 77:335-343, 1965. 8. Russell FE: Marine toxins and venomous and poisonous marine animals, in Advances in marine biology. New York, 1975, Academic Press [nc., vol. 3, pp. 255324. 9. Rosco MD: Cutaneous manifestations of marine animal injuries including diagnosis and treatment. Cutis 19:507-510, 1977. 10. Marowitz NR, Rosenthal RR: Cutaneous-systemic reac-
Journal of the American Academy of Dermatology
Reed et al
tions to toxins and venoms of common marine organisms. Cutis 23:450-454, 1979. 1 t. Black S, Humphrey JH, Niven JSF: Inhibition of Mantoux reaction by direct suggestion under hypnosis. Br Med J 1:1649-1652, 1963. 12. Dvorak HF, Mihm MC, Dvorak AM, et al: Morphology of delayed hypersensitivity reactions in man. I. Quantitative description of the inflammatory response. Lab Invest 31:111-130, 1974.
III II
13. Allen AC: Persistent "insect bites" (dermal eosinophilic granulomas) simulating lymphoblastomas, histiocytoses, and squamous cell carcinomas. Am J Patho124"367-387, 1948. 14. Bemstein H, Shupack J, Ackerman AB: Cutaneous psuedolymphoma resulting from antigen injections. Arch Demaatol 110:756-757, 1974.
I
Cheilitis glandularis: A re-evaluation Robert A. Swerlick, M.D.,*'** and Philip H. Cooper, M.D.*.*** Charlottesville, VA Cheilitis glandularis (CG) has been attributed to hyperplasia of labia/salivary glands. We studied labial biopsy specimens of five patients with clinical CG and compared their salivary tissue with that seen in patients without CG. The labial glands from patients with CG did not differ in size, depth, or histologic appearance from those seen in the controls. They showed little or no inflammation and no hyperplasia. We also reviewed forty-eight cases of CG described in the literature. The accompanying photonficrographs nearly always depicted normal-appearing labial salivary glands. The case histories and clinical descriptions suggested that many examples of CG were manifestations of actinic cheilitis, whereas others may have been unusual presentations of atopic or factitious cheilitis. We believe CG represents an unusual reaction pattern in response to chronic irritation of the lips and is unrelated to labial salivary gland hyperplasia. (J AM ACAD DERMATOL10:466-472, 1984.)
Volkman, ~ in 1870, used the term cheilitis glandularis (CG) to describe a disorder affecting five patients who suffered from deep, suppurative inflammation involving the lower lip. He observed mucopurulent discharge from apparently dilated orifices of salivary ducts and, in addition, severe "catarrhal" inflammation of the mucous memFrom the Departments of Dermatology* and Pathology,*** University of Virginia. Accepted for publicationJuly 11, 1983. Reprint requests to: Dr. Philip H. Cooper, Departmentof Pathology, Box 214, University of Virginia Medical Center, Charlottesville, VA 22908/804-924-5127. **Presently a memberof the faculty of the Department of Dermatology, University of Oklahoma, Oklahoma City, OK.
466
branes of the mouth and pharynx. The presence of inflamed pharyngeal "glands" suggested to Volkman that the disorder of the lips was due to similar inflammation of labial glands. During the subsequent 40 years, additional patients were described with the designation CG, each with a swollen lower lip, prominent salivary duct orifices, and varying degrees of inflammation. 2-7 In one instance, only the upper lip was involved, z Sutton s was the first to suggest the existence of a "slight" form of CG,8 subsequently labeled " C G simplex" by Puente and A c e v e d o ) Their criteria consisted of a slightly enlarged, projecting lower lip with small red points that corresponded to salivary duct openings. Inflammation was minimal or absent.
I |
I
IIIII
i
Ill
Delayed and persistent cutaneous reactions to coelenterates Kenneth M. Reed, M . D . , Ben R. Bronstein, M.D., and Howard P. Baden, M.D.
Boston, MA Three patients are described who developed firm, persistent papules and plaques at sites of previous contact with two species of coelenterates. Histologically, a predominantly mononuclear inflammatory cell infiltrate located primarily in the reticular dermis was observed with destruction of hair follicle epithelium and arrectores pilorum. Epidermal changes included focal spongiosis and exocytosis of lymphocytes. The eruptions subsided no sooner than 7 weeks from time of onset. It is hypothesized that this cutaneous reaction represents a persistent delayed hypersensitivity response to an antigenic component of the coelenterate nematocyst. (J AM ACADDERMATOL 10:462-466, 1984.)
Cutaneous reactions to marine organisms are common but have received little attention in the dermatologic literature. The pathophysiology of the immediate sting reaction has been carefully elaborated with respect to certain marine organisms, t'' However, little information exists concerning the histopathologic events that develop subsequent to the initial sting. Although an acute necrotic response consistent with a sting reaction is most commonly observed initially following contact with coelenterates, a a nonspecific superficial type of acute dermatitis has also been described. 4 Chronic cutaneous reactions to coelenterates have not been well studied. Following Echinoidea (sea urchins) contact, however, a sarcoid-like or foreign b o d y - l i k e granulomatous response has been described after latent periods of up to 12 months s-7 This report describes the hisFrom the Departments of Dermatology and Patllology (Dermatopathology Unit), Harvard Medical School, Massachusetts General Hospital. Accepted for publication Juls' t l , 1983. Reprint requests to: Dr. Howard P. Baden, Department of Dermatology Warren 5, Massachusetts General Hospital, 32 Fruit St., Boston, MA 02114/617-726-3993.
462
topathologic changes in three patients who developed a delayed and persistent cutaneous reaction after contact with coelenterates. CASE REPORTS Case 1 A 28-year-old woman was stung by a jellyfish on her right knee, arm, and cheek while swimming off the Greek island of Mykonos during the month of September. The sites rapidly became erythematous and pruritic but cleared spontaneously within 3 days. After 1 week, erythematous, edematous plaques with a vesicular component developed at sites of previous contact and were treated with a corticosteroid cream (Fig. 1). This therapy did not result in any improvement, and she was placed on a course of prednisone with an initial dose of 60 mg daily that was tapered over 2 weeks and resulted in clearing. However, the lesions recurred several days after stopping the drug. Biopsy of a cheek lesion during the recmTence (2 months after the sting) revealed slight focal hyperkeratosis and diffuse mild spongiosis (Fig. 2). Slight basal layer vacuolization was evident focally. The edematous papillary dermis contained occasional lymphocytes and melanin-laden macrophages, primarily in a perivascular distribution. Within the reticular dermis, a massive infiltrate of small and large lymphocytes and
Volume 10 Number 3 March, 1984
Cutaneous reactions to coelenterates
. ",
463
~ ! ,~i-..i.::~". ) ~ r :;"':4"'r~" " "'.. ". . ~.~j
N Fig. 1. Case 1. A well-demarcated red plaque is seen on
[
the right cheek. occasional histiocytes surrounded numerous dermal vessels and infiltrated between individual collagen bundles (Fig. 2). Interspersed among the small and large lymphocytes were focal nodular collections of large lymphoid cells with cleaved and noncleaved nuclei and some epithelioid-like cells with abundant cytoplasm. These collections resembled germinal centers; however, where epithelioid-like cells were aggregated, early granuloma formation could not be completely excluded (Fig. 2). The lymphohistioeytic infilttzte invaded several hair follicles that demonstrated spongiosis of the outer root sheath epithelium (Fig. 3). No foreign material was noted with the use of incident and polarized light microscopy. The eruption recurred after a second course of prednisone and finally subsided spontaneously 5 months after the initial contact.
Case 2 A 26-year-old woman contacted a file coral while swimming in the Virgin Islands and developed an immediate stinging sensation at points of contact. An erythematous and pruritic papular eruption developed 4 days later on her left leg and ankle. The eruption resolved spontaneously 7 weeks after the time of contact. Biopsy of a papule from the leg obtained 1 month after the sting occurred revealed focal parakeratosis and spongiosis with exocytosis of small lymphocytes. Within the edematous dermis, there was a superficial and deep primarily perivenular lymphohistiocytic infiltrate containing numerous eosinophils. No foreign material was identified with the use of incident and polarized light microscopy.
Fig. 2. Case 1. There is a dense, diffuse lymphohistiocytic infiltrate present primarily within the reticular dermis; focal aggregations of large lymphocytes and epithelioid-like cells are present (arrowheads). Slight spongiosis and exocytosis of Iymphocytes are seen in the overlying epidermis and follicular epithelium (F). (Hematoxylin-eosin stain; original magnification, • 160.)
Case 3 A 29-year-old woman contacted what she thought was a fire coral while snorkeling in the Virgin Islands. Within minutes she developed hivelike lesions that cleared rapidly coincident after taking diphenhydramine. During the next 7 days, a linear arrangement of firm erythematous papules and plaques developed at the sites of contact. The eruption faded spontaneously 2 months after the initial episode. Biopsy of a papule from the leg performed 6 weeks after the contact showed slight, diffuse epidermal spongiosis, with focal exocytosis of small lymphocytes and focal basal layer vacuolization. In the papillary dermis, prominent edema and a perivascular lymphohistiocytic infiltrate were observed. The infiltrate extended to the deeper portions of the dermis disposed about vessels and surrounded and invaded hair tbllicles, eccrine glands, and, most prominently, arrectores pilorum. The latter appeared markedly disrupted by this infiltrate (Fig. 4). No foreign material was identified with the use of incident and polarized microscopy. COMMENT These cases represent cutaneous reactions to members of the phylum Coelenterata, which are delayed in onset and persistent. Of the 9,000 or so
464
Reed et al
r ~ ~,.~.
I
Journal of the American Academy of Dermatology
~""
"~-. ,,
~'~'
.
.
~
"~'
,
~r' ,
~ t~
Fig. 3. Case 1. Within two hair follicles (F) are prominent lymphocytic infiltration and spongiosis. The infiltrating ceils are primarily small lymphocytes. (Hematoxylin-eosin stain; original magnification, x 400.)
species of coelenterates, only about seventy have been implicated in injuries to man or are known to be capable of penetrating human skin. 8 This phylum has been subdivided into three classes. The first, Hydrozoa, includes hydroids, Portuguese man-of-war, and the fire coral (Cases 2 and 3). Scyphozoa comprise the second class of coelenterates and the category to which jellyfish (Case 1) belong. The third class, the Anthozoa, includes sea anemones and true corals? All coelenterates have in common a structure, composed of a capsule and tube, known as the nematocyst. In the capsule is a coiled thread that, when uncoiled and ejected, pierces the skin and discharges its toxic contents through its long filamentous tube? This uncoiling can be triggered by either chemical or mechanical stimuli. Nematocysts are distributed widely in the epidermis of coelenterates and are present in large numbers on the tentacles of these organisms. Once the nematocyst has penetrated the skin, toxins that may be released include quarternary ammonium compounds, proteins, 5-hydroxytryptamine, catecholamines, histamine, and histamine liberators. ~''~ These substances produce the erythema and edema seen in acute sting reactions and contribute to the sensations o f pain and pruritus. However, little is known
Fig. 4. Case 3. This arrector pili has been infiltrated and partially destroyed by the dense mononuclear inflammatory cell infiltrate. (Hematoxylin-eosin stain; original magnification, x 400.) about the incidence of persistent cutaneous reactions to coelenterate stings or about their pathogenesis. In speculating about underlying cellular mechanisms, we recognized that the histologic appearance of the biopsy specimens from our three patients bore certain resemblances to previous histologic studies of delayed hypersensitivity reactions in humans. Black et al I~ examined delayed hypersensitivity reactions occurring after intradermal injection of purified protein derivative of tuberculin and noted primarily a perivascular lymphocytic infiltrate with focal intervenular extension. In a more detailed study Dvorak et al, 12 with the use of sections 1 /~m thick, demonstrated prominent perivascular infiltrates composed primarily oflymphocytes, with some macrophages extending into the deep dermis and subcutis. The infiltrates were less pronounced in the intervascular areas of the dermis. Basophils were observed in approximately 60% of cases, while eosinophils were observed in only two of the thirty-six cases. Using paraffin-embedded hematoxylin and eo-
Volume 10 Number 3 March, 1984
sin- stained sections, we observed a lymphohistiocytic infiltrate centered primarily around dermal venules in Patients 2 and 3. However, in Patient 1, the dermal inflammatory cell infiltrate permeated the intervascular dermis as well. Patient 1 further differed from delayed hypersensitivity reactions by demonstrating prominent infiltration of hair follicles and arrectores pilorum and this was also true for Patient 3. Eosinophils were prominent in the infiltrate only in Patient 2. Basophils cannot be evaluated in routinely processed biopsy specimens. Within the intervenular infiltrates in Patient 1, there were focal aggregates of large mononuclear cells vaguely resembling germinal centers, a finding not observed in the studies of Dvorak et al. t"- Interestingly enough, "pseudolymphoma" has been reported in association with prolonged reactions to insect bites and allergy hyposensitization injections.~3,~4 As in most of the cases reported by Dvorak et al, epidermal changes, including focal spongiosis and infiltration of the epidermis by !ymphocytes, were noted in all three biopsies. These changes may be secondary to the underlying dermal inflammation and edema. Furthermore, in two of the three cases focal hyperkeratosis or parakeratosis was evident, findings which may be related to the chronicity of these lesions. If we hypothesize that the observed tissue reactions are related to a prolonged delayed hypersensitivity (cell-mediated immune) response to intradermally injected antigen, the histologic differences observed between our study and the studies of Black et al 1~and Dvorak et al ~z may be related to the persistent nature of the immunologic response. The reactions in the present cases were documented as late as 2 months after presumed intradermal (and/or subcutaneous) antigen injection. Similarly, cutaneous reactions up to 2 years in duration to arthropod bites have been reported. ~3 The histologic appearances of such lesions differ from those in this study by the presence of a large number of eosinophils, some plasma cells, and prominent epidermal hyperplasia.t3 No nematocysts or other foreign material could be identified in the tissue sections examined by reduced illumination, by polarized light, or with
Cutaneous reactions to coelenterates
465
the reticulin stain. The latter has been found useful in identifying nematocysts, which are impregnated with silver? Foreign body or sarcoid-like granulomatous reactions reported to result from injury by sea urchins, ~'~ were not observed, although some loci in Patient 1 suggested early granuloma formation. The presence and exact nature of the antigen(s) responsible for eliciting the observed inflammatory responses cannot be determined in tissue sections by currently available technics. Therefore, direct evidence for the role of coelenterate antigen(s) in provoking the reactions in these three cases is speculative. A similar mechanism has been suggested by Meneghini* for the delayed component of sea urchin dermatitis. In that study, Meneghini was able to produce a dermal delayed hypersensitivity reaction with the use of intraderreal injection of water-alcohol extracts of sea urchin spines in two fishermen with sea urchin granulomas.* *Meneghini CI: Cases of sea urchin granulomawith positive intradermal test to spine extracts. Contact Dermatitis Newsletter 12:316, 1972. REFERENCES 1. Hashimoto Y: Marine toxins and other bioactive marine metabolites. Tokyo, 1979, Japan Scientific Societies Press. 2. Halstead BW: Poisonous and venomous marine animals of the world. Princeton, NJ, 1978, Darwin Press. 3. Kingston CW, Southcott RV: Skin histopathology in fatal jellyfish stinging. Trans R Soc Trop Med Hyg 54:373-384, 1960. 4. DeOreo GA: Dermatitis venenata resulting from contact with marine animals (hydroids). Arch Derrnatol Syph 54:637-649, 1946. 5. Fisher AA: Dermatitis caused by echi.noderms, in Atlas of aquatic dermatology. New York, 1978, Grune & Stratton Inc., pp. 27-34. 6. Rocha G, Fraga S: Sea urchin granuloma of the skin. Arch Dermatol 85:406-408, 1962. 7. Kinmont PDC: Sea urchin sarcoidal granuloma. Br J Dermatol 77:335-343, 1965. 8. Russell FE: Marine toxins and venomous and poisonous marine animals, in Advances in marine biology. New York, 1975, Academic Press [nc., vol. 3, pp. 255324. 9. Rosco MD: Cutaneous manifestations of marine animal injuries including diagnosis and treatment. Cutis 19:507-510, 1977. 10. Marowitz NR, Rosenthal RR: Cutaneous-systemic reac-
Journal of the American Academy of Dermatology
Reed et al
tions to toxins and venoms of common marine organisms. Cutis 23:450-454, 1979. 1 t. Black S, Humphrey JH, Niven JSF: Inhibition of Mantoux reaction by direct suggestion under hypnosis. Br Med J 1:1649-1652, 1963. 12. Dvorak HF, Mihm MC, Dvorak AM, et al: Morphology of delayed hypersensitivity reactions in man. I. Quantitative description of the inflammatory response. Lab Invest 31:111-130, 1974.
III II
13. Allen AC: Persistent "insect bites" (dermal eosinophilic granulomas) simulating lymphoblastomas, histiocytoses, and squamous cell carcinomas. Am J Patho124"367-387, 1948. 14. Bemstein H, Shupack J, Ackerman AB: Cutaneous psuedolymphoma resulting from antigen injections. Arch Demaatol 110:756-757, 1974.
I
Cheilitis glandularis: A re-evaluation Robert A. Swerlick, M.D.,*'** and Philip H. Cooper, M.D.*.*** Charlottesville, VA Cheilitis glandularis (CG) has been attributed to hyperplasia of labia/salivary glands. We studied labial biopsy specimens of five patients with clinical CG and compared their salivary tissue with that seen in patients without CG. The labial glands from patients with CG did not differ in size, depth, or histologic appearance from those seen in the controls. They showed little or no inflammation and no hyperplasia. We also reviewed forty-eight cases of CG described in the literature. The accompanying photonficrographs nearly always depicted normal-appearing labial salivary glands. The case histories and clinical descriptions suggested that many examples of CG were manifestations of actinic cheilitis, whereas others may have been unusual presentations of atopic or factitious cheilitis. We believe CG represents an unusual reaction pattern in response to chronic irritation of the lips and is unrelated to labial salivary gland hyperplasia. (J AM ACAD DERMATOL10:466-472, 1984.)
Volkman, ~ in 1870, used the term cheilitis glandularis (CG) to describe a disorder affecting five patients who suffered from deep, suppurative inflammation involving the lower lip. He observed mucopurulent discharge from apparently dilated orifices of salivary ducts and, in addition, severe "catarrhal" inflammation of the mucous memFrom the Departments of Dermatology* and Pathology,*** University of Virginia. Accepted for publicationJuly 11, 1983. Reprint requests to: Dr. Philip H. Cooper, Departmentof Pathology, Box 214, University of Virginia Medical Center, Charlottesville, VA 22908/804-924-5127. **Presently a memberof the faculty of the Department of Dermatology, University of Oklahoma, Oklahoma City, OK.
466
branes of the mouth and pharynx. The presence of inflamed pharyngeal "glands" suggested to Volkman that the disorder of the lips was due to similar inflammation of labial glands. During the subsequent 40 years, additional patients were described with the designation CG, each with a swollen lower lip, prominent salivary duct orifices, and varying degrees of inflammation. 2-7 In one instance, only the upper lip was involved, z Sutton s was the first to suggest the existence of a "slight" form of CG,8 subsequently labeled " C G simplex" by Puente and A c e v e d o ) Their criteria consisted of a slightly enlarged, projecting lower lip with small red points that corresponded to salivary duct openings. Inflammation was minimal or absent.