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Loxosceles reclusa spider bite: A consideration in the differential diagnosis of chronic, nonmalignant ulcers of the vulva
Volume Number
Communications
140 3
in brief
341
the drug dosage were not comparable to the usual clinical situation. Naloxone has also been demonstrated to inhibit the release of stress-related prolactin,’ suggesting that the mechanisms may be more complex than proposed. However, the observation that morphine increased survival adds support to the hypothesis that blockage of endorphins is the basic pathophysiology and that naloxone reached the fetuses in therapeutic levels. If the unusual experimental design described in this report is accepted, these data suggest that newborn apnea, even in the absence of narcotic administration, may respond to naloxone but that naloxone administration may also reduce a neonate’s resistance to asphyxia/stress. REFERENCES
1. Nakao, K., Nakai, Y., Jingami, H., et al.: Substantial rise of plasma @ endorphin levels after insulin-induced hypoglycemia in human subjects, J. Clin. Endocrinol. Metab. 49:838, 1979. 2. Wardlaw, S. L., Stark, R. J., Baxi, L., and Frantz, A. G.: Plasma /3-endorphin and p lipotrophin in the human fetus at delivery: Correlation with arterial pH and PO,, J. Clin. Endocrinol. Metab. 49:888, 1979. 3. Goodlin, R. C., and Lloyd, D.: Use of drugs to protect against fetal asphyxia, AM. J. OSSTET. GYNECOL. 10’7:227, 1970. 4. Shnider, S. M., Levinson, G.: Anesthesia for Obstetrics, Baltimore, 1979, The Williams & Wilkins Co., p. 89. 5. Goodlin, R. C.: Naloxone and its possible relationship to fetal endorphin levels and fetal distress, AM. J. OBSTET. GYNECOL. 139:16, 1981. 6. Chernick, V., Madansky, D., and Lawson, E.: Naloxone decreases the duration of primary apnea with neonatal asphyxia, Pediatr. Res. 14:357, 1980. 7. Rossier, J., French, E., Rivier, C., et al.: Blockade by dexamethasone and naloxone may indicate P-endorphin mediation, Proc. Natl. Acad. Sci. USA 77:666, 1980.
Loxosceles reclusa spider bite: A consideration in the differential diagnosis of chronic, nonmalignant ulcers of the vulva
Fig. 1. Large, right labia vulvitis.
necrotic ulceration involving the mons majora, and clitoris; there is an associated
pubis, severe
percentage of such a population. The diagnosis is usually established by bacteriologic, serologic, and/or histologic examination. A review of the literature has revealed that necrotic ulcerations secondary to spider bite are not included in the differential diagnosis of chronic ulcers of the vulva. A case is presented of a patient with a chronic necrotic ulcer of the vulva secondary to Loxosceles reclusa spider bite. The
patient,
a 45-year-old,
para
40-l-4,
white
woman,
was of a chronic ulcer of the vulva of unknown etiology. Her past medical history was significant for pernicious anemia, repeated pulmonary infections requiring hospitalization on several occasions, bronchiectasis, and repeated urinary tract infections. In June, 1977, she experienced pain in the pubic area momentarily, shortly after she finished dressing. That night, she complained of burning and pain and observed swelling and redness of the pubic area. A few days later, she developed a “sore,” followed by blisters, a black eschar, and finally ulceration with aggravation of the pain. She went to her local physician 8 weeks following the formation of the ulcer. Conservative measures, including topical antibiotic and steroid therapy, resulted in no improvement over a period of several weeks. She was referred to a local institution where clinical and lab oratory studies failed to demonstrate an etiologic agent. She
admitted to our institution in September, 1978, because J.
F.
MAGRINA,
B.
J,
MASTERSON,
M.D. M.D.
Department of Obstetrics and Gynecology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas ULCERS AND EROSIONS ofthe vulva accountforalmost half of the patients attending a vulva clinic.’ Chronic, nonmalignant ulcers account for only a small Reprint requests: Dr. J. F. Magrina, Department of Obstetrics and Gynecology, College of Health Sciences and Hospital, University of Kansas, 39th and Rainbow Boulevard, Kansas City, Kansas 66103. 0002-9378/81/110341+03$00.30/0~
1981TheC.V.Mosby
Co.
342
Communications
in brief
Fig. 2. Ulceration with acute matoxylin and eosin. X 25.)
June 1. 1981 Am. .I. Obstet. Gynecol.
and chronic
inflammation.
(He-
was reported as having a necrotic ulcer in the pubis and right paraclitoral area measuring 3 by 3.5 by 0.5 cm. Inguinal nodes were palpated bilaterally. A biopsy of the ulcer was reported as nonspecific acute and chronic inflammation with abscess formation. Biopsy of the enlarged inguinal nodes revealed reactive hyperplasia and chronic inflammation. The lymph nodes became smaller, but the ulcer was unchanged following 4 weeks of antibiotic therapy and topical steroid applications. Prednisone was begun and continued until her admission to our institution, IO months later. During that period, abscess formation in the ulcer base occurred on two occasions and required surgical drainage. Culture of the abscess material revealed Staphylocorrw epidermidis. Reduction of the size of the ulcer was noted 8 months following initiation of steroid therapy. Unfortunately, the ulcer worsened and severe pain, requiring narcotics for relief, persisted. She was then referred to our institutiolt. On admission, temperature was 37.3” C; blood pressure, 124170; pulse, X0 bpm; and respirations, 16/min. Physical examination demonstrated pronounced cushingoid features, wheezing in the pulmonary bases, and a genital necrotic ulcer (Fig. I) as significant findings. The base of the ulcer was covered with fibrinopurulent material and contained multiple miliary abscesses. Blood studies were significant for severe hypogammaglobulinemia (total protein, 4.8 gmldl; albumin, 3. I.?; alpha- I globulin 0.24: alpha-2 globulin 0.62; beta glob-
Fig. 3. Wide
excision
of vulvar
ulcer
and partial
vulvectomy.
ulin, 0.68: gamma globulin, 0.12; IgG, < 100 pgidl; IgA, < 10 pg/dl: IgM < 10 pg/dl). Serology tests, as well as complement fixation titer for lymphogranuloma venereum, histoplasmosis, blastomycosis, coccidioidomycosis, and antinuclear antibodies, were reported as negative. The candida allergy screen skin test was reactive; the purified protein derivative skin test was nonreactive. Cultures of the ulcer exudate demonstrated a few Corynebacterium species. Other studies reported as negative included acid-fast and fungal stain smears, smears for Donovan bodies and Ducrey’s bacillus, cultures and biopsies for herpesvirus, actinomycosis, aspergillosis. cryptococcosis and sporotrichosis, and histologic examination for Donovan bodies. Urine culture revealed Corynebacterium species > IO5 and alpha streptococci < 105. A chest radiogram was suggestive of bronchiectasis. Barium enema revealed no abnormalities. Multiple biopsies of the ulcer revealed acute and chronic inflammation with abscess formation and pseudoepitheliomatous hyperplasia (Fig. 2). She was treated with parenteral antibiotics and fresh frozen plasma, followed by weekly doses of immunogtobulins, on an outpatient basis, to correct her immunodeficiency status and secondary bacterial infection of the ulcer. No improvement was observed over a period of 4 weeks, at which time she presented with acute urinary retention secondary to excruciating vulvar pain and edema. She was readmitted in October, 1978. A wide excision of the ulcer and partial vulvectomy were accomplished (Fig.
Volume Number
Communications
140
in brief
343
3
Fig. 5. One year following wide excision of vulvar ulcer, partial vulvectomy, and application of skin graft. Partial remodeling of mons pubis and minimal scarring are noted.
Fig. 4. Surgical defect following wide excision of vulvar ulcer and partial vulvectomy. 3). The patient noted dramatic and immediate relief of her severe pain. The vulvar defect was left open for granulation and subsequent skin graft (Fig. 4). On the fifteenth erative day, a skin graft was applied. Excellent take tained in 60% of the graft. She was discharged
postopwas obon the
twenty-fifth postoperative day. One year later remodeling of the pubis was present and scarring was minimal (Fig. 5). The diagnosis of chronic, nonmalignant ulcers of the vulva is based on the patient’s history, clinical course, characteristics of the ulcer, presence of associated systemic disorders, and laboratory studies. In a recent study including 375 patients with erosions and ulcers of the vulva, the differential diagnosis included 18 different entities.’ In the case presented, cultures and smears of the ulcer, as well as histologic examination, failed to reveal a specific etiologic agent. The patient’s history, clinical course, and characteristics of the ulcer make Loxosceles reclusa spider bite the most likely diagnosis. The accurate diagnosis is established by the recovery and identification of Loxosceles reclusa spider. However, spider recovery is not always possible and painless bites do occur.** 3, In the absence of identification of the spider, the hemagglutination-inhibition test4 is useful to detect small amounts of venom expressed from the
site. Unfortunately the test is only useful during the first 24 hours following the bite. The lymphocyte transformation test,j although originally encouraging, is no longer used. Since the spider is infrequently retrieved for precise identification2 and many patients are seen later than the first 24 hours, the clinical course and the presence of a typical lesion are considered acceptable to establish the diagnosis.3 In the case reported here, chronic secondary bacterial infection and impairment of the immune response interfered with healing, perpetuating the ulceration. Patients such as ours with common variable hypogammaglobulinemia have a tendency for repeated infections as a result of a decreased immune response. Basic therapy consists of periodic gamma globulin replacement. The use of fresh frozen plasma, gamma globulin, and antibiotics failed to promote healing of the ulceration. Surgical excision with secondary grafting provided a good clinical result. Although identification of the spider was never made, the patient’s history, the clinical course, and the characteristics of the ulcer make Loxosceles reclusa spider bite the most likely diagnosis. REFERENCES 1. Young, A. W., Jr., Tovell, H. M. M., and Sadri, K.: Erosions and ulcers of the vulva. Diagnosis, incidence and management, Obstet. Gynecol. 50:35, 1979. 2. Majeski, J. A., and Durst, G. G., Sr.: Necrotic arachnidism, South. Med. J. 69~887, 1976. 3. Auer, A. I., and Hershey, F. B.: Surgery for necrotic bites of the brown spider, Arch. Surg. 10%:6\2, 1974. 4. Finke, J. H., Campbell, B. J., and Barrett, J. T.: Serodiagnostic test for Loxosceles reclusa bites, Clin. Toxicol. 7:375, 1974. 5. Berger, R. S., Millikan, L. E., and Conway, F.: An in vitro test for Loxosceles reclusa spider bites, Toxicon 11:465, 1973. 6. Hermans, P. E., Diaz-Buxo, J. A., and Stobo, J. D.: Idiopathic late-onset immunoglobulin deficiency, Am. J. Med. 61:221, 1976.
Communications
140 3
in brief
341
the drug dosage were not comparable to the usual clinical situation. Naloxone has also been demonstrated to inhibit the release of stress-related prolactin,’ suggesting that the mechanisms may be more complex than proposed. However, the observation that morphine increased survival adds support to the hypothesis that blockage of endorphins is the basic pathophysiology and that naloxone reached the fetuses in therapeutic levels. If the unusual experimental design described in this report is accepted, these data suggest that newborn apnea, even in the absence of narcotic administration, may respond to naloxone but that naloxone administration may also reduce a neonate’s resistance to asphyxia/stress. REFERENCES
1. Nakao, K., Nakai, Y., Jingami, H., et al.: Substantial rise of plasma @ endorphin levels after insulin-induced hypoglycemia in human subjects, J. Clin. Endocrinol. Metab. 49:838, 1979. 2. Wardlaw, S. L., Stark, R. J., Baxi, L., and Frantz, A. G.: Plasma /3-endorphin and p lipotrophin in the human fetus at delivery: Correlation with arterial pH and PO,, J. Clin. Endocrinol. Metab. 49:888, 1979. 3. Goodlin, R. C., and Lloyd, D.: Use of drugs to protect against fetal asphyxia, AM. J. OSSTET. GYNECOL. 10’7:227, 1970. 4. Shnider, S. M., Levinson, G.: Anesthesia for Obstetrics, Baltimore, 1979, The Williams & Wilkins Co., p. 89. 5. Goodlin, R. C.: Naloxone and its possible relationship to fetal endorphin levels and fetal distress, AM. J. OBSTET. GYNECOL. 139:16, 1981. 6. Chernick, V., Madansky, D., and Lawson, E.: Naloxone decreases the duration of primary apnea with neonatal asphyxia, Pediatr. Res. 14:357, 1980. 7. Rossier, J., French, E., Rivier, C., et al.: Blockade by dexamethasone and naloxone may indicate P-endorphin mediation, Proc. Natl. Acad. Sci. USA 77:666, 1980.
Loxosceles reclusa spider bite: A consideration in the differential diagnosis of chronic, nonmalignant ulcers of the vulva
Fig. 1. Large, right labia vulvitis.
necrotic ulceration involving the mons majora, and clitoris; there is an associated
pubis, severe
percentage of such a population. The diagnosis is usually established by bacteriologic, serologic, and/or histologic examination. A review of the literature has revealed that necrotic ulcerations secondary to spider bite are not included in the differential diagnosis of chronic ulcers of the vulva. A case is presented of a patient with a chronic necrotic ulcer of the vulva secondary to Loxosceles reclusa spider bite. The
patient,
a 45-year-old,
para
40-l-4,
white
woman,
was of a chronic ulcer of the vulva of unknown etiology. Her past medical history was significant for pernicious anemia, repeated pulmonary infections requiring hospitalization on several occasions, bronchiectasis, and repeated urinary tract infections. In June, 1977, she experienced pain in the pubic area momentarily, shortly after she finished dressing. That night, she complained of burning and pain and observed swelling and redness of the pubic area. A few days later, she developed a “sore,” followed by blisters, a black eschar, and finally ulceration with aggravation of the pain. She went to her local physician 8 weeks following the formation of the ulcer. Conservative measures, including topical antibiotic and steroid therapy, resulted in no improvement over a period of several weeks. She was referred to a local institution where clinical and lab oratory studies failed to demonstrate an etiologic agent. She
admitted to our institution in September, 1978, because J.
F.
MAGRINA,
B.
J,
MASTERSON,
M.D. M.D.
Department of Obstetrics and Gynecology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas ULCERS AND EROSIONS ofthe vulva accountforalmost half of the patients attending a vulva clinic.’ Chronic, nonmalignant ulcers account for only a small Reprint requests: Dr. J. F. Magrina, Department of Obstetrics and Gynecology, College of Health Sciences and Hospital, University of Kansas, 39th and Rainbow Boulevard, Kansas City, Kansas 66103. 0002-9378/81/110341+03$00.30/0~
1981TheC.V.Mosby
Co.
342
Communications
in brief
Fig. 2. Ulceration with acute matoxylin and eosin. X 25.)
June 1. 1981 Am. .I. Obstet. Gynecol.
and chronic
inflammation.
(He-
was reported as having a necrotic ulcer in the pubis and right paraclitoral area measuring 3 by 3.5 by 0.5 cm. Inguinal nodes were palpated bilaterally. A biopsy of the ulcer was reported as nonspecific acute and chronic inflammation with abscess formation. Biopsy of the enlarged inguinal nodes revealed reactive hyperplasia and chronic inflammation. The lymph nodes became smaller, but the ulcer was unchanged following 4 weeks of antibiotic therapy and topical steroid applications. Prednisone was begun and continued until her admission to our institution, IO months later. During that period, abscess formation in the ulcer base occurred on two occasions and required surgical drainage. Culture of the abscess material revealed Staphylocorrw epidermidis. Reduction of the size of the ulcer was noted 8 months following initiation of steroid therapy. Unfortunately, the ulcer worsened and severe pain, requiring narcotics for relief, persisted. She was then referred to our institutiolt. On admission, temperature was 37.3” C; blood pressure, 124170; pulse, X0 bpm; and respirations, 16/min. Physical examination demonstrated pronounced cushingoid features, wheezing in the pulmonary bases, and a genital necrotic ulcer (Fig. I) as significant findings. The base of the ulcer was covered with fibrinopurulent material and contained multiple miliary abscesses. Blood studies were significant for severe hypogammaglobulinemia (total protein, 4.8 gmldl; albumin, 3. I.?; alpha- I globulin 0.24: alpha-2 globulin 0.62; beta glob-
Fig. 3. Wide
excision
of vulvar
ulcer
and partial
vulvectomy.
ulin, 0.68: gamma globulin, 0.12; IgG, < 100 pgidl; IgA, < 10 pg/dl: IgM < 10 pg/dl). Serology tests, as well as complement fixation titer for lymphogranuloma venereum, histoplasmosis, blastomycosis, coccidioidomycosis, and antinuclear antibodies, were reported as negative. The candida allergy screen skin test was reactive; the purified protein derivative skin test was nonreactive. Cultures of the ulcer exudate demonstrated a few Corynebacterium species. Other studies reported as negative included acid-fast and fungal stain smears, smears for Donovan bodies and Ducrey’s bacillus, cultures and biopsies for herpesvirus, actinomycosis, aspergillosis. cryptococcosis and sporotrichosis, and histologic examination for Donovan bodies. Urine culture revealed Corynebacterium species > IO5 and alpha streptococci < 105. A chest radiogram was suggestive of bronchiectasis. Barium enema revealed no abnormalities. Multiple biopsies of the ulcer revealed acute and chronic inflammation with abscess formation and pseudoepitheliomatous hyperplasia (Fig. 2). She was treated with parenteral antibiotics and fresh frozen plasma, followed by weekly doses of immunogtobulins, on an outpatient basis, to correct her immunodeficiency status and secondary bacterial infection of the ulcer. No improvement was observed over a period of 4 weeks, at which time she presented with acute urinary retention secondary to excruciating vulvar pain and edema. She was readmitted in October, 1978. A wide excision of the ulcer and partial vulvectomy were accomplished (Fig.
Volume Number
Communications
140
in brief
343
3
Fig. 5. One year following wide excision of vulvar ulcer, partial vulvectomy, and application of skin graft. Partial remodeling of mons pubis and minimal scarring are noted.
Fig. 4. Surgical defect following wide excision of vulvar ulcer and partial vulvectomy. 3). The patient noted dramatic and immediate relief of her severe pain. The vulvar defect was left open for granulation and subsequent skin graft (Fig. 4). On the fifteenth erative day, a skin graft was applied. Excellent take tained in 60% of the graft. She was discharged
postopwas obon the
twenty-fifth postoperative day. One year later remodeling of the pubis was present and scarring was minimal (Fig. 5). The diagnosis of chronic, nonmalignant ulcers of the vulva is based on the patient’s history, clinical course, characteristics of the ulcer, presence of associated systemic disorders, and laboratory studies. In a recent study including 375 patients with erosions and ulcers of the vulva, the differential diagnosis included 18 different entities.’ In the case presented, cultures and smears of the ulcer, as well as histologic examination, failed to reveal a specific etiologic agent. The patient’s history, clinical course, and characteristics of the ulcer make Loxosceles reclusa spider bite the most likely diagnosis. The accurate diagnosis is established by the recovery and identification of Loxosceles reclusa spider. However, spider recovery is not always possible and painless bites do occur.** 3, In the absence of identification of the spider, the hemagglutination-inhibition test4 is useful to detect small amounts of venom expressed from the
site. Unfortunately the test is only useful during the first 24 hours following the bite. The lymphocyte transformation test,j although originally encouraging, is no longer used. Since the spider is infrequently retrieved for precise identification2 and many patients are seen later than the first 24 hours, the clinical course and the presence of a typical lesion are considered acceptable to establish the diagnosis.3 In the case reported here, chronic secondary bacterial infection and impairment of the immune response interfered with healing, perpetuating the ulceration. Patients such as ours with common variable hypogammaglobulinemia have a tendency for repeated infections as a result of a decreased immune response. Basic therapy consists of periodic gamma globulin replacement. The use of fresh frozen plasma, gamma globulin, and antibiotics failed to promote healing of the ulceration. Surgical excision with secondary grafting provided a good clinical result. Although identification of the spider was never made, the patient’s history, the clinical course, and the characteristics of the ulcer make Loxosceles reclusa spider bite the most likely diagnosis. REFERENCES 1. Young, A. W., Jr., Tovell, H. M. M., and Sadri, K.: Erosions and ulcers of the vulva. Diagnosis, incidence and management, Obstet. Gynecol. 50:35, 1979. 2. Majeski, J. A., and Durst, G. G., Sr.: Necrotic arachnidism, South. Med. J. 69~887, 1976. 3. Auer, A. I., and Hershey, F. B.: Surgery for necrotic bites of the brown spider, Arch. Surg. 10%:6\2, 1974. 4. Finke, J. H., Campbell, B. J., and Barrett, J. T.: Serodiagnostic test for Loxosceles reclusa bites, Clin. Toxicol. 7:375, 1974. 5. Berger, R. S., Millikan, L. E., and Conway, F.: An in vitro test for Loxosceles reclusa spider bites, Toxicon 11:465, 1973. 6. Hermans, P. E., Diaz-Buxo, J. A., and Stobo, J. D.: Idiopathic late-onset immunoglobulin deficiency, Am. J. Med. 61:221, 1976.