British Journal of Dermatology (1977), 96, 205.

An unusual presentation of Trichophyton violaceum infection A.KAMALAM, PATRICK YESUDIAN AND A.S.THAMBIAH Madras Medical College and Government General Hospital, Madras, India Accepted for publication 12 July 1976

SUMMARY

A case with encapsulated Tricophyton violaceum abscesses in the skin is recorded. Defective cell mediated immunity was shown in the patient and in his two cousins. This defect combined with malnutrition, hypoadrcnalism and griseofulvin resistance gave unusual lesions and chronicity. A probable genetic factor for the defective cell mediated immunity is postulated.

Ringworm infections, though characteristically superficial, have in rare cases been demonstrated in viable tissues like dermis, lymph nodes, bones and other organs (Verbov, 1973; Araviysky, Araviysky & Eschkov, 1975; Blank & Smith, i960). Haematogenous dissemination in some cases has been postulated. We report a case of Trichophyton violaceum involving the dermis and subcutis. The roles of malnutrition, hypoadrenalism and defective immune response are discussed. Conventional antifungal therapy was unsuccessful. CASE REPORT

An ii-year-old boy, a pinman with generalized scaly skin and multiple cutaneous swellings, was admitted to our Department in November 1969. His illness started at the age of 3 months as a small patch of ringworm on his chest. Gradually skin elsewhere, scalp and nails were involved. By the 9th or ioth year cutaneous swellings appeared over the trunk. On admission he had a wizened look, peevish, poorly built but mentally alert. He showed heavy crusting from scalp to toes, rough palms and soles, and lobulated and globular swellings over the interscapular and pectoral regions—the largest on the back of 9 x 45 cm size (Fig. i). All nails were greyish-black, with subungual hyperkcratosis. Sparse hairs were present on the scalp, eyebrows and eyelids with no lanugo hairs anywhere. Inguinal and axillary lymph nodes were enlarged, discrete and non-tender. A soft systolic murmur over the precordium, a few rhonchi and rales over the chest, and soft liver enlargement of 6 cm were observed. Other systems were normal. Laboratory findings

RBC2-3I X io''/mm^; Hb 55%;WBCiOj6oo/mm-';neutrophils4O%;lymphocytes34/;;cosinophils 205

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A.Kamalam, P.Yesudian and A.S.Thambiah

FIGURE I. Globular cystic swelling left shoulder with tinea corporis. FIGURE 2. Pus under coverslip showing septate hyphae with branching ( x 750). FIGURE 3. Early nodule showing chlamydospores and septate hyphae across giant cells in the dermis (PAS, x 750). FIGURE 4. Early nodule showing the granuloma close to the epidermis and absence of capsule (H& E, x8s).

25%; monocytes 1%; absolute eosinophil count 255o/mm-'; ESR 14 mm/h. Routine examinations of stools, urine, blood urea, blood uric acid, VDRL test, serum cholesterol, serum calcium and serum proteins were normal. Glucose tolerance test showed the following; fasting 81 mg "„; ^ h loi mg "(,; 1 h t38 mg "„; i^ h 133 mg "„ and 2 h 125 mg "„ with no glycosuria. X-rays of skull, spine and abdomen were normal but that of the chest showed a calcified primary complex, widened mediastinum and a soft tissue shadow from the skin tumour. Skin scrapings from several sites showed Acariis scabiei and fungal mycelia; the latter were also present in the finger and toe nails. His scalp hair showed an cndothrix infection. Trichophyton violacemn was isolated on Sabouraud's dextrose agar from skin, hair and nails. Biopsy of one of tbe nodules (H & E stain) showed an acanthotic epidermis.

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circumscribed foci of inflammatory cells (histiocytes and plasma cells) independently and around blood vessels in the middle and upper dermis, and areas of fibrosis. Periodic acid Schiff (PAS) stain was not done at this time. A diagnosis of generalized dermatophytosis and crusted scabies with underlying malnutrition was made. He was treated with 10",, sulphur ointment for 3 days followed by 3"^, sulphur and salicylic ointment along with 375 mg of griseofulvin and 150 mg of INAH daily for 3 months. A high protein diet with added vitamins and iron was given. His skin condition and hair growth improved considerably but his nails showed little or no change. The skin up to his elbows and knees was pigmented and lichenified in a glove and stocking fashion. The swellings regressed partially. At this stage systemic and topical therapy was continued as an outpatient. After a year he was further investigated as fresh nodules had appeared over his trunk above the umbilicus, arms and neck. After periods ranging from 4 months to 2^ years the cystic nodules broke down spontaneously exuding thick, viscid odourless pus containing plenty of septate hyphae (Fig. 2) and chains of chlamydospores. Trichophyton violaceum was cultured several times from this pus without any admixture of bacteria. It grew well at 37 C and exhibited proteolytic activity in casein agar (Emmons, Binford & Utz, 1970). Studies with H&E, PAS and Gomori's methanamine silver (GMS) stains of an early nodule showed an acanthotic epidermis, a dermal giant cell granuloma mainly of foreign body type, plasma cells, histiocytes and eosinophils. Plenty of septate hyphae and chlamydospores in and outside giant cells were seen throughout the dermis (Fig. 3). There was no capsule (Fig. 4), and no fungus in the epidermis. An alcian blue stain (Graham, 1972) showed increased alcian blue positive material especially around the fungal elements. A disrupted hair follicle in the midst of the granuloma without any hair structure or keratin was seen with an acid fast stain. A well developed freely mobile nodule studied in a similar way showed 3 distinct layers consisting ofa fibrous capsule, a subcapsular giant cell layer (mainly of foreign body type) containing the fungus, and an inner layer of histiocytes, plasma cells, neutrophils, eosinophils and a moderate number of hyphae and chlamydospores. In certain areas these fungal hyphae were seen in aggregates to resemble the grains of mycetoma. Necrotic eosinophilic granular material with hyphae and chlamydospores was seen in the central area. The junction between the giant cell layer and the inner mixed cell layer contained the fungal elements. The suspected lymph node at the root of the neck proved on histological sections and culture to be fibrous and muscle tissues containing the fungus. Peripheral and antecubital vein blood failed to grow the fungus. Chronic generalized trichophytosis with subcutaneous abscesses not responding to conventional therapy warranted endocrinological and immunological studies. His lymphocytes exposed to PHA failed to transform into blast cells, different dilutions of tuberculin failed to evoke any reaction and there was persistent eosinophilia. The trichophytin test was not done as the antigen was not available. Urinary 17-ketosteroids before (57 mg 24 h) and after (63 mg 24 h) ACTH showed very little difference. With Schilling's test 16% of vitamin B , , introduced was excreted compared with the normal 6% in the control. Serum potassium and sodium were normal. Chromosomal study was normal. The serum inhibitory effect (Blank et al, 1959; Lorincz, Priestley & Jacobs, 1958) against dermatophytes was normal. Pus from the nodule was injected intradermally (05 ml) into the inner aspect of the hind limbs and subcutaneously (i ml) into the fianks ofa rabbit and a guinea-pig. Viability of the pus was ascertained on Sabouraud's dextrose agar at the same time. The rabbit developed a freely mobile subcutaneous nodule in the flank by the 2nd day, which enlarged to 2 x i cm in 2 months and then regressed. Pus from this nodule showed non-viable fragmented irregular granular hyphae. Histologically the nodule was a capsulated granuloma with PAS positive granular deposits suggesting destroyed fungal elements. The 05 cm nodule on the 2nd day in the guinea-pig's flank regressed by the H

A.Kamalam, P.Yesudian and A.S.Thambiah 4th day and by the 15th day showed alopecia. The hair from this site grew T. simii. The nodules in the hind hmbs of both animals regressed completely by the loth day. A sensitivity test to griseofulvin (Young, 1972) was done with the isolates obtained before and 3 years after starting treatment. The minimum inhibitory concentration (MIC) was 39 /(g/ml and complete inhibition occurred at the 15-62 /Jg/ml concentration with the initial isolate. The corresponding values for the post-treatment isolate were 31 25 //g/ml and 125 /fg/tnl. Two of his first cousins (a male of 18 and a female of 15 years) were found to have generalized dermatophytosis due to T. violaceitm but without the fungal abscesses. The boy in addition had borderline leprosy and the girl had generalized lymph node enlargement and a thickened right pinna without evidence of fungus in these tissues. Persistent eosinophilia, absence of tuberculin reaction and failure of lymphoblast transformation were also observed in both. Their serum protein profile and serum inhibitory factor against dermatophyte (Blank et al, 1959) were normal. Chromosomal study was not done. Topical Whitfield's ointment and oral griseofulvin gave satisfactory results in 3 months. Fainting attacks with low blood sugar level (60-80 mg%) was observed in our patient. The incompletely evacuated nodules refilled with pus but scarring resulted in completely evacuated ones. White lunules and leukonychia of infected thumb and index fingers occurred while on treatment. Whitfield's ointment, phytoderm (Kamalam & Thambiah, 1972), tolnaftate and miconazole were useful but lesions recurred after withdrawal of these drugs. Glutaraldehyde and tincture of iodine were useless. The griseofulvin dosage was increased to i g daily with no improvement and prednisolone 5 mg daily was added. His growth and body weight have improved since admission but he appears short statured and dark complexioned. He is being followed for further developments. DISCUSSION

Deep seated and fatal disseminated granulomatous trichophytoses have been reported (Brit & Wilt, 1954; Spencer 1954; Blank et al, 1959; Blank & Smith, i960; Shetsivali & Arievitch, 1968; Beare, Gentles & Mackenzie, 1972; Araviysky, Araviysky & Eschkov, 1975). Lymphatic or haematogenous spread suggested in some of these cases was associated with reduced general resistance against infection due to debilitating diseases. Repeated demonstration of T. violaceum in the viable tissues of dermis, muscle of neck and lunule while on treatment suggests a lymphatic or haematogenous spread in the present case, but the absence of invasion of the wall of the nodules, blood vessels or epidermis and the destroyed or remnant hair follicle in the dermis suggest rupture of an infected hair follicle, introducing the fungus into the dermis. It is also probable that the Acarus scabiei would have aided deeper penetration. A low titre of fungistatic activity of serum, long term use of steroids, and rheumatoid arthritis as reported by Blank et al (i960) were not contributory factors here but investigations revealed hypoadrenalism. A 2 h blood glucose level of 125 mg "/,, may also suggest a high skin glucose level as occurs with 'cutaneous glycohistechis' and skin diabetes (Rothman, 1955)- This could not be proved by a skin glucose tolerance test. The clinical and histological features observed in our case are similar to those reported by Araviysky et al. (1975). The response to experimental animal inoculation and the absence of deep seated lesions in the cousins of the patient denote an altered host response to the fungus. The negative tuberculin response, absent visceral and id lesions, failure of blast transformation, normal serum inhibitory factor against dermatophytes, and normal protein profile point towards a defective cell mediated immunity or a defective lymphocyte system. This defective cell mediated immunity in all 3 bloodrelated individuals is an indication of a specific genetic, probably autosomal dominant, abnormality of defence against trichophytosis as none had candidosis or pyogenic infections.

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ACKNOWLEDGMENTS We are thankful to Dr L.N.Mohapatra of New Delhi, All India Institute of Medical Sciences and Dr L.Ajello of Atlanta, Georgia, for confirming the fungus, Dr L.Chettur of Madras University for genetic studies and Dr Yogeswari, Institute of Venereology, Madras Medical College for help in the lymphoblast transformation test. Glaxo Laboratories (India) Ltd supplied the griseofulvin. REFERENCES ARAVIYSKY A.N., ARAYIVSKY, R.A. & ESCHKOV, G.A. (1975) Deep generalized Trichophytosis. Mycopathohgia, 56, 47BEARE, J.M,, GENTLES, J.C. & MACKENZIE, D . W . R . (1972) Mycology, In: Textbook of Dermatology ((Ed. by

A.J.Rook, D.S.Wilkinson & F.J.Ebling) ist edn, Vol. i, p. 694. Biackwell Scientific Publications, Oxford. BLANK, H., SAGAMI, S., CAROLYN & ROTH, F.J. (1959) The pathogenesis of superficial fungus infections in cul-

tured human skin. Archives of Dermatology, 79, 524. BLANK, H . & SMITH, G.J. (i960) Widespread Trichophyton rubrum granulomas treated with griseofulvin. Archives of Dermatology, 81, 779. BRIT, A.R. & WILT, J.C. (1954) Mycology, bacteriology and histopaihology of suppurative ringworm. Archives of Dermatology & Syphilology, 69, 441. EMMONS, C.W., BINFORD, C.H. & UTZ, J.P. (1970) Culture media. In: Medical Mycology. 2nd edn, p. 464. Lea & Febiger, Philadelphia. GRAHAM, J.H. (1972) Superficial fungus infections. In: Dermal pathology (Ed. by J.H.Graham, W.C.Johnson & E.B.Helwig), p. 137. Harper & Row, New York. KAMALAM, A. & THAMBIAH, A.S. (1972) A trial of phyroderm in superficial fungus infection. Antiseptic, 69, 871. LoRiNCz, A.L., PRIESTLEY, J.O. & JACOBS, P.H. (1958) Evidence for a humoral mechanism which prevents growth of dermatophytes.,/"W'"^' of Investigative Dermatology, 31, 15. ROTHMAN, S. (1955) Carbohydrates, In: Physiology and Biochemistry of [he Skin, p. 465. The University of Chicago Press, Chicago. SHETSIVALI, L . T . & ARIEVITCH, A.N. (1968) On the pathogenesis of generalized forms of mycosis caused by epidermophyton rubrum. Mycopathohgia et Mycohgial applicata, 35, 184. SPENCER, M . C . (1954) Congenital ichthyosiform erythroderma. Tinea capitis and tinea corporis—Trichophyton violaceum. Archives of Dermatology, 69, 751. VERBOV, J. (1973) Granulomatous Trichophyton rubrum infection of the pinnae. British Journal of Dermatology, 89, 212.

YOUNG, C . N . (1972) Sensitivity patterns to griseofulvin of Trichophyton rubrum and other ringworm fungi. Transactions of the Stjohi's Hospital Dermatological Society, s8, 226.

An unusual presentation of Trichophyton violaceum infection.

British Journal of Dermatology (1977), 96, 205. An unusual presentation of Trichophyton violaceum infection A.KAMALAM, PATRICK YESUDIAN AND A.S.THAMB...
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