Clinical and Experimental Dermatology 1992; 17: 44 46.
Bullous secondary syphilis P.LAWRENCE AND N.SAXE* Groote Schiuir Hospital! University of Cape Ftjwn, Observatory, 7925 Cape Town, Soath .Africa Accepted for publication 28 April 1991
Summary An earlier standard syphilology textbook states that 'If vesicles are an essential part of an eruption in an adult, the lesions are not due to secondary syphilis'.' However, vesicular and bullous eruptions do occur in congenital syphilis and rare reports ot both vesicular- and pustular' eruptions in adults with secondary syphilis ha\e been published. We describe a patient with a bullous-pemphigoid-likc eruption and a positive VDRL in whom treatment with a course of procaine penicillin resulted in rapid permanent resolution ofthe eruption. Case report A 40-year-old man was referred with a widespread, mildly pruritic blistering eruption of two weeks duration. He was generally well except for a hoarse voice and bilateral non-tender shotty inguinal lymphadenopathy. On examination of the skin, clear fluid-filled bullae, many with necrotic centres, were distributed randomly on his trunk and limbs (Fig. 1). In addition, macerated papules in the intertrigenous zones, and annular perioral lesions were present {I'ig. 2). The latter feature suggested the diagnosis of syphilis.^ Otolaryngological examination revealed normal mucosal surfaces with slight erythema of the vocal cords. On histological examination of an intact blister, a unilocular sub-cpidermal vesicle was present witb a superficial perivascular lymphoeytie inflltrate and occasional eosinophils and plasma cells in the upper dermis (Fig. 3). A Warthin-Starry stain failed to reveal any spirochaetes. Direct immunofluorescence of peri-lesional skin showed linear deposits of IgG and C.}i at the basement membrane zone. Indirect immunofluorescence of tbe serum for anti-basement membrane antibody and antiepithelial antibody was negative. Tbese bistological and immunofluorescence findings were similar to those found in bullous pempbigoid.
To whom correspondence should be addressed.
44
Figure 1. A close-up of mainlv iniaci Inillac on the trunk and axilhi. Manv show central necrosis.
A VDRL test was positive to a dilution of 1:32. Tbe TPH.A test was also positive. Normal results were seen in tbe following investigations: baemoglobin, white cell count, platelets, differential count, erythrocyte sedimentation rate., urea and electrolytes, liver function tests, total complement, C3 and C4 anti-nuclear antibody, rbeumatoid factor, cbest X-ray and urinalysis. A diagnosisof tbe secondary stage of sypbilis, based on
BULLOUS SECONDARY SYPHILIS
45
Figure 2. Perioral annular lesions highly ,suggcsti\e of secondary syphitis.
organism in the lesions of secondary syphitis other than condylomata lata;^ only one-third of cases of secondary syphilis may show the spiroehaete.'' Tbe presence of pathognomonic perioral papules suggested the diagnosis clinically, despite the atypical truncal rash. A VDRL result positive to a titre of 32 with a positive TPHA test is regarded as adequate (if indirect) evidence of active . - : • , % ; • ••.i;v-'£.'^^''^ •.-^-'/••j^v/-... syphilis. When the clinical features are atypical, careful correlation of historical, laboratory and clinieal features is necessary to exclude the possibility of a co-incidental cutaneous eruption with a pre-existing positive VDRL.' In short, tbe perioral papules, positive serology and rapid, complete resolution of tbe skin lesions on penicillin alone, left little clinical doubt as to the aetiological 3. Lnilocubr subepidermal vesicle indistinfjuishable from connection between the patient's rash and his positive bullous pemphigoid (H & F. x 4(1). VDRL We were not able to perform a follow-up VDRL on tbis the perioral annular lesions and positive serology was patient, although we were informed tbat be bad no made and a lO-day course of intramuscular procaine further problems at a 2-year follow-up visit to his own penicillin was instituted. .-MI the skin lesions resolved doctor. A drop in VDRL titre following treatment would rapidl\ within two weeks ofthe initiation of therapy. No not have served to attribute this patient's skin lesions to other medication was prescribed. Tbe patient has not had sypbilis, as the titre ofthe VDRL would drop on pencillin any recurrence of the rash during the 2 years following treatment, regardless of whether or not the eruption was due to syphilis. Equally, whether or not the patient is treatment. treated, the VDRL titre will drop as the syphilis progresses from the secondary to the latent stage. Discussion The intriguing feature of this case was the unusual The cutaneous manifestations ofthe secondary stage of bullous lesions wbose histological appearances and direct syphilis are protean and include bullous lesions despite immunofluorescence findings in the peri-lesionai skin were similar to tbose occurring in bullous pemphigoid. claims to tbe contrary."-' The diagnosis of secondary syphilis in this patient Such a bullous eruption has not been described prewould have been irrefutable bad dark-field examination viously in secondary sypbilis. One study did document been performed to demonstrate tbe presence of tbe immunoreactants (including IgG and C3) m the dermal spirochaete. The negative Warthin-Stnrry stain does not vessels of cutaneous lesions of secondary sypbilis but negate tbe diagnosis as it is difficult to demonstrate the none were present at the basement membrane zone."
46
P.LAWRKNCE AND N.SAXE
Syphilis has not previously been considered in the differential diagnosis of linear deposits of IgG and C3 at the basement membrane zone. In evaluating the clinical picture, serology and therapeutic response of this patient it is unlikely that the patient had hullous pemphigoid; in particular we have not found any previous report of hullous pemphigoid responding to treatment with penicillin. If, as we believe, this patient's skin lesions were due to syphilis, we remain unable to explain the clinical, histologicai and direct immunofluorescencc similarities of this patient's skin lesions to those of bullous pemphigoid. Further studies on the immunofluorescence of the cutaneous lesions of secondary syphilis may prove useful. Acknowledgment We thank Dr D.Roditi, Department of Medical Microbiology, University of C^apetown, for reading the manuscript and providing helpful advice.
References 1. Stoke.s JH, Becrman H, Ingraham NR Jr. Modern clinical syphilology. diagnosis treaiment. case study. (3rci Kd). Philadelphia;
Saunders, 1945, 527. 2. I Iowles JK. A synopsis ofclinnat syphilis. St Louis: Mosby, 1943, 73-74. 3. Mindel A, Tovey SJ, Timmins DJ, Williams P. Primary and Secondary Syphilis, 20 years experience. Genitourinary Meiltcme 1989; 65: 1-3. 4. Rosen T, Martin S, Alias of Black Dermalology. Boston: Little, Brown and (^ompan>, 19HI, 46 47. 5. Mehregen Amir H. Pinkus' Guide lo Dermalohistopathology (4th edn). Xorwalk, C^onnccticut: Applcton-C;cnttiry-(>()fts, 1986, 264. 6. Lever, Walter F. Schaumherg-Lcvcr Gitndula. Histopathology of the shn (6th edn). Philadelphia: JB Lippineott Co., 1983, .122. 7. Holmes KK, xMardh PA, Sparling ?V, Wiesner PJ. Sexually transmitted diseases. New York: McGraw-Hill Book Company, 1984, 310-311. 8. McNcely CM, Jorizzo JL, Solomon AR, Smith LB, C:avallo T, Sanchez RL. Cutaneous secondary syphilis: Prcliniinar\ immunohistopathologit support for a role for immune complexes in lesion pathogenesis. Journal of ihe American Academy of Dermatoloi^y
1986; 14: 564-571.
Bullous secondary syphilis P.LAWRENCE AND N.SAXE* Groote Schiuir Hospital! University of Cape Ftjwn, Observatory, 7925 Cape Town, Soath .Africa Accepted for publication 28 April 1991
Summary An earlier standard syphilology textbook states that 'If vesicles are an essential part of an eruption in an adult, the lesions are not due to secondary syphilis'.' However, vesicular and bullous eruptions do occur in congenital syphilis and rare reports ot both vesicular- and pustular' eruptions in adults with secondary syphilis ha\e been published. We describe a patient with a bullous-pemphigoid-likc eruption and a positive VDRL in whom treatment with a course of procaine penicillin resulted in rapid permanent resolution ofthe eruption. Case report A 40-year-old man was referred with a widespread, mildly pruritic blistering eruption of two weeks duration. He was generally well except for a hoarse voice and bilateral non-tender shotty inguinal lymphadenopathy. On examination of the skin, clear fluid-filled bullae, many with necrotic centres, were distributed randomly on his trunk and limbs (Fig. 1). In addition, macerated papules in the intertrigenous zones, and annular perioral lesions were present {I'ig. 2). The latter feature suggested the diagnosis of syphilis.^ Otolaryngological examination revealed normal mucosal surfaces with slight erythema of the vocal cords. On histological examination of an intact blister, a unilocular sub-cpidermal vesicle was present witb a superficial perivascular lymphoeytie inflltrate and occasional eosinophils and plasma cells in the upper dermis (Fig. 3). A Warthin-Starry stain failed to reveal any spirochaetes. Direct immunofluorescence of peri-lesional skin showed linear deposits of IgG and C.}i at the basement membrane zone. Indirect immunofluorescence of tbe serum for anti-basement membrane antibody and antiepithelial antibody was negative. Tbese bistological and immunofluorescence findings were similar to those found in bullous pempbigoid.
To whom correspondence should be addressed.
44
Figure 1. A close-up of mainlv iniaci Inillac on the trunk and axilhi. Manv show central necrosis.
A VDRL test was positive to a dilution of 1:32. Tbe TPH.A test was also positive. Normal results were seen in tbe following investigations: baemoglobin, white cell count, platelets, differential count, erythrocyte sedimentation rate., urea and electrolytes, liver function tests, total complement, C3 and C4 anti-nuclear antibody, rbeumatoid factor, cbest X-ray and urinalysis. A diagnosisof tbe secondary stage of sypbilis, based on
BULLOUS SECONDARY SYPHILIS
45
Figure 2. Perioral annular lesions highly ,suggcsti\e of secondary syphitis.
organism in the lesions of secondary syphitis other than condylomata lata;^ only one-third of cases of secondary syphilis may show the spiroehaete.'' Tbe presence of pathognomonic perioral papules suggested the diagnosis clinically, despite the atypical truncal rash. A VDRL result positive to a titre of 32 with a positive TPHA test is regarded as adequate (if indirect) evidence of active . - : • , % ; • ••.i;v-'£.'^^''^ •.-^-'/••j^v/-... syphilis. When the clinical features are atypical, careful correlation of historical, laboratory and clinieal features is necessary to exclude the possibility of a co-incidental cutaneous eruption with a pre-existing positive VDRL.' In short, tbe perioral papules, positive serology and rapid, complete resolution of tbe skin lesions on penicillin alone, left little clinical doubt as to the aetiological 3. Lnilocubr subepidermal vesicle indistinfjuishable from connection between the patient's rash and his positive bullous pemphigoid (H & F. x 4(1). VDRL We were not able to perform a follow-up VDRL on tbis the perioral annular lesions and positive serology was patient, although we were informed tbat be bad no made and a lO-day course of intramuscular procaine further problems at a 2-year follow-up visit to his own penicillin was instituted. .-MI the skin lesions resolved doctor. A drop in VDRL titre following treatment would rapidl\ within two weeks ofthe initiation of therapy. No not have served to attribute this patient's skin lesions to other medication was prescribed. Tbe patient has not had sypbilis, as the titre ofthe VDRL would drop on pencillin any recurrence of the rash during the 2 years following treatment, regardless of whether or not the eruption was due to syphilis. Equally, whether or not the patient is treatment. treated, the VDRL titre will drop as the syphilis progresses from the secondary to the latent stage. Discussion The intriguing feature of this case was the unusual The cutaneous manifestations ofthe secondary stage of bullous lesions wbose histological appearances and direct syphilis are protean and include bullous lesions despite immunofluorescence findings in the peri-lesionai skin were similar to tbose occurring in bullous pemphigoid. claims to tbe contrary."-' The diagnosis of secondary syphilis in this patient Such a bullous eruption has not been described prewould have been irrefutable bad dark-field examination viously in secondary sypbilis. One study did document been performed to demonstrate tbe presence of tbe immunoreactants (including IgG and C3) m the dermal spirochaete. The negative Warthin-Stnrry stain does not vessels of cutaneous lesions of secondary sypbilis but negate tbe diagnosis as it is difficult to demonstrate the none were present at the basement membrane zone."
46
P.LAWRKNCE AND N.SAXE
Syphilis has not previously been considered in the differential diagnosis of linear deposits of IgG and C3 at the basement membrane zone. In evaluating the clinical picture, serology and therapeutic response of this patient it is unlikely that the patient had hullous pemphigoid; in particular we have not found any previous report of hullous pemphigoid responding to treatment with penicillin. If, as we believe, this patient's skin lesions were due to syphilis, we remain unable to explain the clinical, histologicai and direct immunofluorescencc similarities of this patient's skin lesions to those of bullous pemphigoid. Further studies on the immunofluorescence of the cutaneous lesions of secondary syphilis may prove useful. Acknowledgment We thank Dr D.Roditi, Department of Medical Microbiology, University of C^apetown, for reading the manuscript and providing helpful advice.
References 1. Stoke.s JH, Becrman H, Ingraham NR Jr. Modern clinical syphilology. diagnosis treaiment. case study. (3rci Kd). Philadelphia;
Saunders, 1945, 527. 2. I Iowles JK. A synopsis ofclinnat syphilis. St Louis: Mosby, 1943, 73-74. 3. Mindel A, Tovey SJ, Timmins DJ, Williams P. Primary and Secondary Syphilis, 20 years experience. Genitourinary Meiltcme 1989; 65: 1-3. 4. Rosen T, Martin S, Alias of Black Dermalology. Boston: Little, Brown and (^ompan>, 19HI, 46 47. 5. Mehregen Amir H. Pinkus' Guide lo Dermalohistopathology (4th edn). Xorwalk, C^onnccticut: Applcton-C;cnttiry-(>()fts, 1986, 264. 6. Lever, Walter F. Schaumherg-Lcvcr Gitndula. Histopathology of the shn (6th edn). Philadelphia: JB Lippineott Co., 1983, .122. 7. Holmes KK, xMardh PA, Sparling ?V, Wiesner PJ. Sexually transmitted diseases. New York: McGraw-Hill Book Company, 1984, 310-311. 8. McNcely CM, Jorizzo JL, Solomon AR, Smith LB, C:avallo T, Sanchez RL. Cutaneous secondary syphilis: Prcliniinar\ immunohistopathologit support for a role for immune complexes in lesion pathogenesis. Journal of ihe American Academy of Dermatoloi^y
1986; 14: 564-571.
